Variant 4-68929908-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024743.4(UGT2A3):c.1489G>A(p.Ala497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,612,308 control chromosomes in the GnomAD database, including 554,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42135 hom., cov: 31)

Exomes 𝑓: 0.83 ( 512543 hom. )

Consequence

UGT2A3
NM_024743.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Variant links:

Genes affected

UGT2A3 (HGNC:28528): (UDP glucuronosyltransferase family 2 member A3) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT2A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3052224E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT2A3	NM_024743.4 linkuse as main transcript	c.1489G>A	p.Ala497Thr	missense_variant	6/6	ENST00000251566.9
UGT2A3	XM_011532247.3 linkuse as main transcript	c.1507G>A	p.Ala503Thr	missense_variant	6/6
UGT2A3	XM_047416177.1 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	6/6
UGT2A3	NR_024010.2 linkuse as main transcript	n.1630G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A3	ENST00000251566.9 linkuse as main transcript	c.1489G>A	p.Ala497Thr	missense_variant	6/6	1	NM_024743.4	P1
UGT2A3	ENST00000503012.1 linkuse as main transcript	c.*665G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.731

AC:

110912

AN:

151770

Hom.:

42124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.830

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.802

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.858

Gnomad OTH

AF:

0.736

GnomAD3 exomes

AF:

0.760

AC:

190300

AN:

250414

Hom.:

74627

AF XY:

0.777

AC XY:

105140

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.547

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.675

Gnomad SAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.853

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.833

AC:

1216615

AN:

1460420

Hom.:

512543

Cov.:

AF XY:

0.835

AC XY:

606429

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.850

Gnomad4 EAS exome

AF:

0.666

Gnomad4 SAS exome

AF:

0.814

Gnomad4 FIN exome

AF:

0.738

Gnomad4 NFE exome

AF:

0.867

Gnomad4 OTH exome

AF:

0.809

GnomAD4 genome

AF:

0.730

AC:

110951

AN:

151888

Hom.:

42135

Cov.:

AF XY:

0.726

AC XY:

53855

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.531

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.856

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.804

Gnomad4 FIN

AF:

0.740

Gnomad4 NFE

AF:

0.858

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.814

Hom.:

28138

Bravo

AF:

0.710

TwinsUK

AF:

0.874

AC:

3241

ALSPAC

AF:

0.862

AC:

3324

ESP6500AA

AF:

0.545

AC:

2403

ESP6500EA

AF:

0.859

AC:

7384

ExAC

AF:

0.765

AC:

92930

Asia WGS

AF:

0.714

AC:

2485

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.039

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

REVEL

Benign

0.22

Sift

Benign

0.15

Sift4G

Benign

0.14

Polyphen

0.63

Vest4

0.015

MPC

0.017

ClinPred

0.039

GERP RS

2.2

Varity_R

0.048

gMVP

0.088

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