Variant 2-233617864-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019076.5(UGT1A8):c.157C>A(p.His53Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000432 in 1,614,072 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

UGT1A8
NM_019076.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

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:

UGT1A (HGNC:):

UGT1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018691868).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A8	NM_019076.5 linkuse as main transcript	c.157C>A	p.His53Asn	missense_variant	1/5	ENST00000373450.5	NP_061949.3	Q9HAW9-1Q5DSZ6
UGT1A	use as main transcript	n.233617864C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.157C>A	p.His53Asn	missense_variant	1/5	1	NM_019076.5	ENSP00000362549.4		Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

368

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00836

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000621

AC:

156

AN:

251396

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00800

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152194

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00836

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000684

Hom.:

Bravo

AF:

0.00272

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000807

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.019

MetaSVM

Uncertain

-0.035

MutationAssessor

Pathogenic

3.0

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.30

Sift

Benign

0.044

Sift4G

Uncertain

0.051

Polyphen

0.85

Vest4

0.77

MVP

0.84

ClinPred

0.12

GERP RS

4.0

Varity_R

0.40

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over