rs13128286

Positions:

• chr4-68929908-C-G
• chr4-68929908-C-T

Variant summary

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

The NM_024743.4(UGT2A3):​c.1489G>C​(p.Ala497Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

Genes affected

UGT2A3 (HGNC:28528): (UDP glucuronosyltransferase family 2 member A3) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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	UniProt
UGT2A3	NM_024743.4	c.1489G>C	p.Ala497Pro	missense_variant	6/6	ENST00000251566.9
UGT2A3	XM_011532247.3	c.1507G>C	p.Ala503Pro	missense_variant	6/6
UGT2A3	XM_047416177.1	c.622G>C	p.Ala208Pro	missense_variant	6/6
UGT2A3	NR_024010.2	n.1630G>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A3	ENST00000251566.9	c.1489G>C	p.Ala497Pro	missense_variant	6/6	1	NM_024743.4	P1
UGT2A3	ENST00000503012.1	c.*665G>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.057	N
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.8	H
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.75		Loss of stability (P = 0.1909);
MVP		0.69
MPC		0.023
ClinPred		0.92	D
GERP RS		2.2
Varity_R		0.59
gMVP		0.48

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

Other links and lift over

dbSNP: rs13128286; hg19: chr4-69795626;