NM_024743.4:c.1489G>A

Variant names:

• chr4-68929908-C-T
• rs13128286
• NM_024743.4:c.1489G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024743.4(UGT2A3):​c.1489G>A​(p.Ala497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,612,308 control chromosomes in the GnomAD database, including 554,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (42135 hom., cov: 31)
  • Exomes 𝑓: 0.83 (512543 hom.)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3052224E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024743.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A3	NM_024743.4	MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 6 of 6	NP_079019.3
	UGT2A3	NR_024010.2		n.1630G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A3	ENST00000251566.9	TSL:1 MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 6 of 6	ENSP00000251566.4
	UGT2A3	ENST00000503012.1	TSL:2	n.*665G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000424092.1
	UGT2A3	ENST00000503012.1	TSL:2	n.*665G>A		3_prime_UTR	Exon 7 of 7	ENSP00000424092.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110912 AN: 151770 Hom.: 42124 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.736

GnomAD2 exomes AF: 0.760 AC: 190300 AN: 250414 AF XY: 0.777

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.547

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.675

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.853

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.833 AC: 1216615 AN: 1460420 Hom.: 512543 Cov.: 50 AF XY: 0.835 AC XY: 606429 AN XY: 726538

African (AFR) AF: 0.513 AC: 17153 AN: 33422

American (AMR) AF: 0.561 AC: 25016 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 22187 AN: 26110

East Asian (EAS) AF: 0.666 AC: 26433 AN: 39660

South Asian (SAS) AF: 0.814 AC: 70129 AN: 86172

European-Finnish (FIN) AF: 0.738 AC: 39385 AN: 53386

Middle Eastern (MID) AF: 0.796 AC: 4578 AN: 5752

European-Non Finnish (NFE) AF: 0.867 AC: 962917 AN: 1110978

Other (OTH) AF: 0.809 AC: 48817 AN: 60328

GnomAD4 genome AF: 0.730 AC: 110951 AN: 151888 Hom.: 42135 Cov.: 31 AF XY: 0.726 AC XY: 53855 AN XY: 74226

African (AFR) AF: 0.531 AC: 21982 AN: 41412

American (AMR) AF: 0.659 AC: 10037 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2967 AN: 3468

East Asian (EAS) AF: 0.677 AC: 3468 AN: 5124

South Asian (SAS) AF: 0.804 AC: 3867 AN: 4812

European-Finnish (FIN) AF: 0.740 AC: 7809 AN: 10556

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58299 AN: 67960

Other (OTH) AF: 0.732 AC: 1548 AN: 2114

Alfa AF: 0.776 Hom.: 38078

Bravo AF: 0.710

TwinsUK AF: 0.874 AC: 3241

ALSPAC AF: 0.862 AC: 3324

ESP6500AA AF: 0.545 AC: 2403

ESP6500EA AF: 0.859 AC: 7384

ExAC AF: 0.765 AC: 92930

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.039	N
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.22
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.63	P
Vest4		0.015
MPC		0.017
ClinPred		0.039	T
GERP RS		2.2
Varity_R		0.048
gMVP		0.088
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13128286; hg19: chr4-69795626; COSMIC: COSV52358702;