rs3806596

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019093.4(UGT1A3):​c.-66T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,610,256 control chromosomes in the GnomAD database, including 184,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: 𝑓 0.55 ( 25689 hom., cov: 33)
Exomes 𝑓: 0.46 ( 158654 hom. )

Consequence

UGT1A3
NM_019093.4 5_prime_UTR

Scores

2

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: -4.45
Variant links:
Genes affected
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]
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]
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]
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]
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]
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]
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UGT1A3NM_019093.4 linkuse as main transcriptc.-66T>C 5_prime_UTR_variant 1/5 ENST00000482026.6
UGT1A6NM_001072.4 linkuse as main transcriptc.861+35196T>C intron_variant ENST00000305139.11
UGT1A4NM_007120.3 linkuse as main transcriptc.867+9374T>C intron_variant ENST00000373409.8
UGT1A10NM_019075.4 linkuse as main transcriptc.856-37973T>C intron_variant ENST00000344644.10
UGT1A8NM_019076.5 linkuse as main transcriptc.856-37973T>C intron_variant ENST00000373450.5
UGT1A7NM_019077.3 linkuse as main transcriptc.856-37973T>C intron_variant ENST00000373426.4
UGT1A5NM_019078.2 linkuse as main transcriptc.867+15203T>C intron_variant ENST00000373414.4
UGT1A9NM_021027.3 linkuse as main transcriptc.856-37973T>C intron_variant ENST00000354728.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UGT1A3ENST00000482026.6 linkuse as main transcriptc.-66T>C 5_prime_UTR_variant 1/51 NM_019093.4 P1P35503-1
UGT1A6ENST00000305139.11 linkuse as main transcriptc.861+35196T>C intron_variant 1 NM_001072.4 P1P19224-1
UGT1A10ENST00000344644.10 linkuse as main transcriptc.856-37973T>C intron_variant 1 NM_019075.4 P1Q9HAW8-1
UGT1A9ENST00000354728.5 linkuse as main transcriptc.856-37973T>C intron_variant 1 NM_021027.3 P1O60656-1
UGT1A4ENST00000373409.8 linkuse as main transcriptc.867+9374T>C intron_variant 1 NM_007120.3 P1P22310-1
UGT1A5ENST00000373414.4 linkuse as main transcriptc.867+15203T>C intron_variant 1 NM_019078.2 P1P35504-1
UGT1A7ENST00000373426.4 linkuse as main transcriptc.856-37973T>C intron_variant 1 NM_019077.3 P1Q9HAW7-1
UGT1A8ENST00000373450.5 linkuse as main transcriptc.856-37973T>C intron_variant 1 NM_019076.5 P1Q9HAW9-1

Frequencies

GnomAD3 genomes
AF:
0.555
AC:
84356
AN:
152104
Hom.:
25643
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.819
Gnomad AMI
AF:
0.481
Gnomad AMR
AF:
0.483
Gnomad ASJ
AF:
0.541
Gnomad EAS
AF:
0.329
Gnomad SAS
AF:
0.601
Gnomad FIN
AF:
0.487
Gnomad MID
AF:
0.519
Gnomad NFE
AF:
0.437
Gnomad OTH
AF:
0.515
GnomAD4 exome
AF:
0.459
AC:
669360
AN:
1458036
Hom.:
158654
Cov.:
55
AF XY:
0.463
AC XY:
335625
AN XY:
725180
show subpopulations
Gnomad4 AFR exome
AF:
0.832
Gnomad4 AMR exome
AF:
0.472
Gnomad4 ASJ exome
AF:
0.543
Gnomad4 EAS exome
AF:
0.288
Gnomad4 SAS exome
AF:
0.600
Gnomad4 FIN exome
AF:
0.472
Gnomad4 NFE exome
AF:
0.439
Gnomad4 OTH exome
AF:
0.479
GnomAD4 genome
AF:
0.555
AC:
84450
AN:
152220
Hom.:
25689
Cov.:
33
AF XY:
0.553
AC XY:
41128
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.819
Gnomad4 AMR
AF:
0.483
Gnomad4 ASJ
AF:
0.541
Gnomad4 EAS
AF:
0.329
Gnomad4 SAS
AF:
0.600
Gnomad4 FIN
AF:
0.487
Gnomad4 NFE
AF:
0.437
Gnomad4 OTH
AF:
0.516
Alfa
AF:
0.512
Hom.:
3399
Bravo
AF:
0.563
Asia WGS
AF:
0.478
AC:
1663
AN:
3478

ClinVar

Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Levothyroxine response Other:1
other, no assertion criteria providedresearchPharmacogenomics/Precision medicine lab, University of Petra-- The TT genotype of this SNP in our study was associated with lower levels of T4 after levothyroxine replacement

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.095
DANN
Benign
0.51

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.

Other links and lift over

dbSNP: rs3806596; hg19: chr2-234637707; COSMIC: COSV59390325; COSMIC: COSV59390325; API