Variant 5-36039693-T-C 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.859A>G(p.Ile287Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,990 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UGT3A2
NM_174914.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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:

Genome browser will be placed here

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=0.119998336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT3A2	NM_174914.4 linkuse as main transcript	c.859A>G	p.Ile287Val	missense_variant	5/7	ENST00000282507.8	NP_777574.2
UGT3A2	NM_001168316.2 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	4/6		NP_001161788.1
UGT3A2	XM_011513988.2 linkuse as main transcript	c.940A>G	p.Ile314Val	missense_variant	6/8		XP_011512290.1
UGT3A2	NR_031764.2 linkuse as main transcript	n.420A>G		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A2	ENST00000282507.8 linkuse as main transcript	c.859A>G	p.Ile287Val	missense_variant	5/7	1	NM_174914.4	ENSP00000282507	P1	Q3SY77-1
UGT3A2	ENST00000513300.5 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	4/6	2		ENSP00000427404		Q3SY77-2
UGT3A2	ENST00000504954.1 linkuse as main transcript	n.510A>G		non_coding_transcript_exon_variant	4/4	4
UGT3A2	ENST00000504685.5 linkuse as main transcript	c.327A>G	p.Ser109=	synonymous_variant, NMD_transcript_variant	4/6	2		ENSP00000426017

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Jun 12, 2023

The c.859A>G (p.I287V) alteration is located in exon 5 (coding exon 5) of the UGT3A2 gene. This alteration results from a A to G substitution at nucleotide position 859, causing the isoleucine (I) at amino acid position 287 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.0053

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

0.54

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.23

Sift

Benign

0.60

T;T

Sift4G

Benign

0.62

T;T

Polyphen

1.0

D;.

Vest4

0.22

MutPred

0.69

Gain of ubiquitination at K289 (P = 0.1008);.;

MVP

0.030

MPC

0.27

ClinPred

0.59

GERP RS

3.0

Varity_R

0.049

gMVP

0.21

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