Variant chr5-36048971-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174914.4(UGT3A2):c.761C>A(p.Ala254Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UGT3A2
NM_174914.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT3A2	NM_174914.4 linkuse as main transcript	c.761C>A	p.Ala254Asp	missense_variant	4/7	ENST00000282507.8	NP_777574.2
UGT3A2	NM_001168316.2 linkuse as main transcript	c.659C>A	p.Ala220Asp	missense_variant	3/6		NP_001161788.1
UGT3A2	XM_011513988.2 linkuse as main transcript	c.842C>A	p.Ala281Asp	missense_variant	5/8		XP_011512290.1
UGT3A2	NR_031764.2 linkuse as main transcript	n.404+2899C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A2	ENST00000282507.8 linkuse as main transcript	c.761C>A	p.Ala254Asp	missense_variant	4/7	1	NM_174914.4	ENSP00000282507	P1	Q3SY77-1
UGT3A2	ENST00000513300.5 linkuse as main transcript	c.659C>A	p.Ala220Asp	missense_variant	3/6	2		ENSP00000427404		Q3SY77-2
UGT3A2	ENST00000504685.5 linkuse as main transcript	c.311+2899C>A		intron_variant, NMD_transcript_variant		2		ENSP00000426017
UGT3A2	ENST00000504954.1 linkuse as main transcript	n.494+2899C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 06, 2023

The c.761C>A (p.A254D) alteration is located in exon 4 (coding exon 4) of the UGT3A2 gene. This alteration results from a C to A substitution at nucleotide position 761, causing the alanine (A) at amino acid position 254 to be replaced by an aspartic acid (D). 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

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0089

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0096

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.63

N;.

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.27

Sift

Benign

0.34

T;T

Sift4G

Benign

0.21

T;T

Polyphen

1.0

D;.

Vest4

0.73

MutPred

0.66

Loss of sheet (P = 0.0228);.;

MVP

0.36

MPC

0.34

ClinPred

0.86

GERP RS

3.5

Varity_R

0.21

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over