Variant 5-35955668-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000274278.8(UGT3A1):c.1272G>A(p.Met424Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,614,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

UGT3A1
ENST00000274278.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.817

Variant links:

Genes affected

UGT3A1 (HGNC:26625): (UDP glycosyltransferase family 3 member A1) Enables glucuronosyltransferase activity. Part of UDP-N-acetylglucosamine transferase complex. [provided by Alliance of Genome Resources, Apr 2022]

UGT3A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031102091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT3A1	NM_152404.4 linkuse as main transcript	c.1272G>A	p.Met424Ile	missense_variant	6/7	ENST00000274278.8	NP_689617.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A1	ENST00000274278.8 linkuse as main transcript	c.1272G>A	p.Met424Ile	missense_variant	6/7	1	NM_152404.4	ENSP00000274278	P1	Q6NUS8-1
UGT3A1	ENST00000503189.5 linkuse as main transcript	c.1272G>A	p.Met424Ile	missense_variant	6/6	2		ENSP00000427079
UGT3A1	ENST00000507113.5 linkuse as main transcript	c.1170G>A	p.Met390Ile	missense_variant	5/5	2		ENSP00000426100
UGT3A1	ENST00000515801.5 linkuse as main transcript	c.*2243G>A		3_prime_UTR_variant, NMD_transcript_variant	7/8	2		ENSP00000427630

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000231

AC:

AN:

251474

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000223

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000340

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Jan 04, 2022

The c.1272G>A (p.M424I) alteration is located in exon 6 (coding exon 6) of the UGT3A1 gene. This alteration results from a G to A substitution at nucleotide position 1272, causing the methionine (M) at amino acid position 424 to be replaced by an isoleucine (I). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0048

T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.67

N;.;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;B;P

Vest4

0.29

MutPred

0.68

Gain of ubiquitination at K425 (P = 0.1181);Gain of ubiquitination at K425 (P = 0.1181);.;

MVP

0.13

MPC

0.030

ClinPred

0.035

GERP RS

3.3

Varity_R

0.24

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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