Variant 5-36038001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174914.4(UGT3A2):c.1091G>A(p.Arg364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00003 in 1,600,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

UGT3A2
NM_174914.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.277

Variant links:

Genes affected

UGT3A2 (HGNC:27266): (UDP glycosyltransferase family 3 member A2) Enables UDP-glycosyltransferase activity. Acts upstream of or within cellular response to genistein. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT3A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20961493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT3A2	NM_174914.4 linkuse as main transcript	c.1091G>A	p.Arg364His	missense_variant	6/7	ENST00000282507.8
UGT3A2	NM_001168316.2 linkuse as main transcript	c.989G>A	p.Arg330His	missense_variant	5/6
UGT3A2	XM_011513988.2 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	7/8
UGT3A2	NR_031764.2 linkuse as main transcript	n.652G>A		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT3A2	ENST00000282507.8 linkuse as main transcript	c.1091G>A	p.Arg364His	missense_variant	6/7	1	NM_174914.4	P1	Q3SY77-1
UGT3A2	ENST00000513300.5 linkuse as main transcript	c.989G>A	p.Arg330His	missense_variant	5/6	2			Q3SY77-2
UGT3A2	ENST00000504685.5 linkuse as main transcript	c.*196G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000592

AC:

AN:

236294

Hom.:

AF XY:

0.0000471

AC XY:

AN XY:

127506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000963

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000390

Gnomad SAS exome

AF:

0.0000744

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1448750

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

720180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000963

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000601

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000497

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

Mar 01, 2024

The c.1091G>A (p.R364H) alteration is located in exon 6 (coding exon 6) of the UGT3A2 gene. This alteration results from a G to A substitution at nucleotide position 1091, causing the arginine (R) at amino acid position 364 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.045

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.0091

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.12

Sift

Benign

0.061

T;D

Sift4G

Benign

0.067

T;T

Polyphen

0.57

P;.

Vest4

0.23

MVP

0.16

MPC

0.11

ClinPred

0.23

GERP RS

2.5

Varity_R

0.055

gMVP

0.37

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over