2-233636584-G-C

Position:

chr2-233636584-G-C

Variant summary

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

The NM_019075.4(UGT1A10):c.62G>C(p.Gly21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000854 in 1,614,138 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 3 hom. )

Consequence

UGT1A10
NM_019075.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

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:

UGT1A (HGNC:):

UGT1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02806294).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A10	NM_019075.4 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/5	ENST00000344644.10	NP_061948.1	Q9HAW8-1Q5DT02
UGT1A8	NM_019076.5 linkuse as main transcript	c.855+18022G>C		intron_variant		ENST00000373450.5	NP_061949.3	Q9HAW9-1Q5DSZ6
UGT1A	use as main transcript	n.233636584G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UGT1A10	ENST00000344644.10 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/5	1	NM_019075.4	ENSP00000343838.5	Q9HAW8-1
UGT1A10	ENST00000373445.1 linkuse as main transcript	c.62G>C	p.Gly21Ala	missense_variant	1/5	1		ENSP00000362544.1	Q9HAW8-2
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.855+18022G>C		intron_variant		1	NM_019076.5	ENSP00000362549.4	Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000660

AC:

166

AN:

251360

Hom.:

AF XY:

0.000655

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000871

AC:

1274

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000854

AC XY:

621

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000690

AC:

105

AN:

152254

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000751

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000807

AC:

EpiCase

AF:

0.00202

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.62G>C (p.G21A) alteration is located in exon 1 (coding exon 1) of the UGT1A10 gene. This alteration results from a G to C substitution at nucleotide position 62, causing the glycine (G) at amino acid position 21 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

0.082

Eigen_PC

Benign

-0.010

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.5

L;L

PROVEAN

Benign

-1.6

N;D

REVEL

Benign

0.25

Sift

Benign

0.43

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.96

D;.

Vest4

0.42

MVP

0.57

MPC

0.14

ClinPred

0.045

GERP RS

3.8

Varity_R

0.048

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over