chr2-233772413-T-G

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PP5_Very_Strong

The NM_007120.3(UGT1A4):c.1459T>G(p.Tyr487Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000985 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y487Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

UGT1A4
NM_007120.3 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:16

Conservation

PhyloP100: 5.97

Publications

92 publications found

Variant links:

COSMIC-nc: COSV105895892

Genes affected

UGT1A4 (HGNC:12536): (UDP glucuronosyltransferase family 1 member A4) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins. [provided by RefSeq, Jul 2008]

UGT1A4 links:

UGT1A5 (HGNC:12537): (UDP glucuronosyltransferase family 1 member A5) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. [provided by RefSeq, Jul 2008]

UGT1A5 links:

UGT1A3 (HGNC:12535): (UDP glucuronosyltransferase family 1 member A3) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq, Jul 2008]

UGT1A3 links:

UGT1A1 (HGNC:12530): (UDP glucuronosyltransferase family 1 member A1) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]

UGT1A1 links:

UGT1A6 (HGNC:12538): (UDP glucuronosyltransferase family 1 member A6) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]

UGT1A6 links:

UGT1A10 (HGNC:12531): (UDP glucuronosyltransferase family 1 member A10) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity on mycophenolic acid, coumarins, and quinolines. [provided by RefSeq, Jul 2008]

UGT1A10 links:

UGT1A8 (HGNC:12540): (UDP glucuronosyltransferase family 1 member A8) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity with many substrates including coumarins, phenols, anthraquinones, flavones, and some opioids. [provided by RefSeq, Jul 2008]

UGT1A8 links:

UGT1A7 (HGNC:12539): (UDP glucuronosyltransferase family 1 member A7) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has moderate glucuronidase activity with phenols. [provided by RefSeq, Jul 2008]

UGT1A7 links:

UGT1A9 (HGNC:12541): (UDP glucuronosyltransferase family 1 member A9) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols. [provided by RefSeq, Jul 2008]

UGT1A9 links:

UGT1A (HGNC:12529):

UGT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PP5

Variant 2-233772413-T-G is Pathogenic according to our data. Variant chr2-233772413-T-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 12281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A4	NM_007120.3 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	ENST00000373409.8	NP_009051.1	P22310-1
UGT1A5	NM_019078.2 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	ENST00000373414.4	NP_061951.1	P35504-1Q5DSZ9
UGT1A3	NM_019093.4 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	ENST00000482026.6	NP_061966.1	P35503-1Q5DT01
UGT1A1	NM_000463.3 link	c.1456T>G	p.Tyr486Asp	missense_variant	Exon 5 of 5	ENST00000305208.10	NP_000454.1	P22309-1Q5DT03
UGT1A6	NM_001072.4 link	c.1453T>G	p.Tyr485Asp	missense_variant	Exon 5 of 5	ENST00000305139.11	NP_001063.2	P19224-1Q5DSZ8
UGT1A10	NM_019075.4 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	ENST00000344644.10	NP_061948.1	Q9HAW8-1Q5DT02
UGT1A8	NM_019076.5 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	ENST00000373450.5	NP_061949.3	Q9HAW9-1Q5DSZ6
UGT1A7	NM_019077.3 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	ENST00000373426.4	NP_061950.2	Q9HAW7-1Q5DSZ7
UGT1A9	NM_021027.3 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	ENST00000354728.5	NP_066307.1	O60656-1Q5DSZ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UGT1A4	ENST00000373409.8 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	1	NM_007120.3	ENSP00000362508.4	P22310-1
UGT1A5	ENST00000373414.4 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	1	NM_019078.2	ENSP00000362513.3	P35504-1
UGT1A3	ENST00000482026.6 link	c.1459T>G	p.Tyr487Asp	missense_variant	Exon 5 of 5	1	NM_019093.4	ENSP00000418532.1	P35503-1
UGT1A1	ENST00000305208.10 link	c.1456T>G	p.Tyr486Asp	missense_variant	Exon 5 of 5	1	NM_000463.3	ENSP00000304845.5	P22309-1
UGT1A6	ENST00000305139.11 link	c.1453T>G	p.Tyr485Asp	missense_variant	Exon 5 of 5	1	NM_001072.4	ENSP00000303174.6	P19224-1
UGT1A10	ENST00000344644.10 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	1	NM_019075.4	ENSP00000343838.5	Q9HAW8-1
UGT1A9	ENST00000354728.5 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	1	NM_021027.3	ENSP00000346768.4	O60656-1
UGT1A7	ENST00000373426.4 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	1	NM_019077.3	ENSP00000362525.3	Q9HAW7-1
UGT1A8	ENST00000373450.5 link	c.1447T>G	p.Tyr483Asp	missense_variant	Exon 5 of 5	1	NM_019076.5	ENSP00000362549.4	Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000223

AC:

AN:

251172

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00199

AC:

AN:

39700

South Asian (SAS)

AF:

0.000487

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1112012

Other (OTH)

AF:

0.0000993

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00271

AC:

AN:

5172

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000500

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:4

Jul 19, 2022

Mayo Clinic Laboratories, Mayo Clinic

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PP3, PP5, PM1, PS3, PS4_moderate -

Jun 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 486 of the UGT1A1 protein (p.Tyr486Asp). This variant is present in population databases (rs34993780, gnomAD 0.2%). This variant has been observed in individual(s) with hyperbilirubinemia. Individuals homozygous for this variant present with Gilbert syndrome or Crigler-Najjar syndrome type II (PMID: 18419642, 22169899, 29137095). This variant is sometimes seen on the same chromosome (in cis) with p.Gly71Arg in some individuals affected with Crigler-Najjar syndrome type II (PMID: 9630669, 21297505, 21319362, 24749086). This variant is also known as UGT1A1*7. ClinVar contains an entry for this variant (Variation ID: 12281). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UGT1A1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects UGT1A1 function (PMID: 12181437). For these reasons, this variant has been classified as Pathogenic. -

Jul 26, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Crigler-Najjar syndrome, type II

Pathogenic:4

Jan 03, 2022

3billion

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000012281, PMID:8280139, PS1_S). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25993113, PM3_M). It was co-segregated with Crigler-Najjar syndrome, type II in multiple affected family members (PP1_P). Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product(PMID: 18004206, PS3_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.894, PP3_P). A missense variant is a common mechanism associated with Crigler-Najjar syndrome (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000216, PM2_M).herefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. -

Neuberg Centre For Genomic Medicine, NCGM

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Tyr486Asp variant in UGT1A1 (NM_000463.3) has been reported in the homozygous or compound heterogygous state in numerous individuals with Gilbert syndrome or Crigler-Najjar syndrome type II (Maruo et al, 2000). Functional studies have reported a reduction in enzyme activity (Udomuksorn W et al). It has been submitted to ClinVar as a Pathogenic/Likely Pathogenic variant. The p.Y486D variant is observed at a relatively high frequency in 32/18,394 (0.174%) alleles from individuals of East Asian background in gnomAD Exomes and in 3/1,008 (0.2976%) alleles from individuals of East Asian background in 1000 Genomes. The p.Y486D missense variant is predicted to be damaging by both SIFT and PolyPhen2. The tyrosine residue at codon 486 of UGT1A1 is conserved in all mammalian species. The nucleotide c.1456 in UGT1A1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic -

Dec 01, 2007

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jun 09, 2020

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Tyr486Asp variant in UGT1A1 (variant also known as UGT1A1*7) has been reported in the homozygous or compound heterogygous state in numerous individuals with Gilbert syndrome or Crigler-Najjar syndrome type II (Maruo 2000 PMID: 11061796, Kraemer 2002 PMID: 11983459, Takeuchi 2004 PMID: 15304120, Maruo 2016 PMID: 26250421, Sun 2017 PMID 29137095). The majority of p.Tyr486Asp homozygous individuals with Gilbert syndrome or Crigler-Najjar syndrome type II also carry the p.Gly71Arg variant in the heterozygous or homozygous state. This variant has also been reported in ClinVar (Variation ID 12281). It has been identified in 0.1% (36/19954) of East Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that this variant impacts protein function (Takahashi 2008 PMID: 18816295, Gagne 2002 PMID: 12181437, Jinno 2003 PMID: 12485959); however, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Crigler-Najjar syndrome type II. ACMG/AMP Criteria applied: PS3_Moderate, PM2_Supporting, PP3, PM3_Strong. -

Gilbert syndrome

Pathogenic:2

Dec 19, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2019

Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing You An Hospital, Capital Medical University

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Crigler-Najjar syndrome type 1;C0017551:Gilbert syndrome;C0270210:Lucey-Driscoll syndrome;C1866173:BILIRUBIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 1;C2931132:Crigler-Najjar syndrome, type II

Pathogenic:2

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PM3_VeryStrong+PP1+PS3 -

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lucey-Driscoll syndrome

Pathogenic:1

Dec 01, 2007

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

UGT1A1-related disorder

Pathogenic:1

Aug 08, 2024

PreventionGenetics, part of Exact Sciences

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

The UGT1A1 c.1456T>G variant is predicted to result in the amino acid substitution p.Tyr486Asp. This variant has been reported to be causative for Crigler-Najjar syndrome or Gilbert syndrome when present in the homozygous state. Functional studies showed that the substitution p.Tyr486Asp dramatically reduced UGT1A1 enzyme activity (see, for example, Aono et al. 1993. PubMed ID: 8280139; Yamamoto et al. 1998. PubMed ID: 9630669; Nakagawa et al. 2012. PubMed ID: 23279026; Gagné et al. 2002. PubMed ID: 12181437). This variant has also been found to be causative for Crigler-Najjar syndrome type II in the compound heterozygous state (Luo et al. 2023. PubMed ID: 37137832). This variant is reported in 0.18% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic. -

Hyperbilirubinemia

Pathogenic:1

Apr 10, 2014

Genetic Services Laboratory, University of Chicago

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Crigler-Najjar syndrome type 1

Pathogenic:1

Sep 22, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;D;D;D;.;D;D;D;D;D

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.68

MutationAssessor

Pathogenic

4.2

.;.;H;.;.;.;.;.;.;.

PhyloP100

6.0

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.3

D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;D;D;D;D

Vest4

0.96

MVP

0.94

MPC

0.25, 0.43, 0.70, 0.68, 0.93, 0.25, 0.24, 0.74

ClinPred

0.46

GERP RS

5.8

Varity_R

0.82

gMVP

0.79

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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