Variant 5-36039683-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_174914.4(UGT3A2):c.869T>C(p.Phe290Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UGT3A2
NM_174914.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850

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 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=0.054197103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT3A2	NM_174914.4 linkuse as main transcript	c.869T>C	p.Phe290Ser	missense_variant	5/7	ENST00000282507.8
UGT3A2	NM_001168316.2 linkuse as main transcript	c.767T>C	p.Phe256Ser	missense_variant	4/6
UGT3A2	XM_011513988.2 linkuse as main transcript	c.950T>C	p.Phe317Ser	missense_variant	6/8
UGT3A2	NR_031764.2 linkuse as main transcript	n.430T>C		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT3A2	ENST00000282507.8 linkuse as main transcript	c.869T>C	p.Phe290Ser	missense_variant	5/7	1	NM_174914.4	P1	Q3SY77-1
UGT3A2	ENST00000513300.5 linkuse as main transcript	c.767T>C	p.Phe256Ser	missense_variant	4/6	2			Q3SY77-2
UGT3A2	ENST00000504954.1 linkuse as main transcript	n.520T>C		non_coding_transcript_exon_variant	4/4	4
UGT3A2	ENST00000504685.5 linkuse as main transcript	c.337T>C	p.Leu113=	synonymous_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251396

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 06, 2021

The c.869T>C (p.F290S) alteration is located in exon 5 (coding exon 5) of the UGT3A2 gene. This alteration results from a T to C substitution at nucleotide position 869, causing the phenylalanine (F) at amino acid position 290 to be replaced by a serine (S). 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

0.34

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.0074

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

1.7

N;N

REVEL

Benign

0.18

Sift

Benign

0.070

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.50

P;.

Vest4

0.15

MutPred

0.74

Loss of methylation at K289 (P = 0.0316);.;

MVP

0.11

MPC

0.37

ClinPred

0.30

GERP RS

1.8

Varity_R

0.053

gMVP

0.30

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