rs142020441

Variant names:

• chr4-68931191-G-A
• rs142020441
• NM_024743.4:c.1048C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-68931191-G-A
• chr4-68931191-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024743.4(UGT2A3):​c.1048C>T​(p.Arg350Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R350Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A3	NM_024743.4	MANE Select	c.1048C>T	p.Arg350Trp	missense	Exon 4 of 6	NP_079019.3
	UGT2A3	NR_024010.2		n.1189C>T		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A3	ENST00000251566.9	TSL:1 MANE Select	c.1048C>T	p.Arg350Trp	missense	Exon 4 of 6	ENSP00000251566.4	Q6UWM9
	UGT2A3	ENST00000852414.1		c.1066C>T	p.Arg356Trp	missense	Exon 4 of 6	ENSP00000522473.1
	UGT2A3	ENST00000852415.1		c.916C>T	p.Arg306Trp	missense	Exon 3 of 5	ENSP00000522474.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250950 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460844 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726708

African (AFR) AF: 0.000120 AC: 4 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39634

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86210

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53390

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111388

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151954 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74206

African (AFR) AF: 0.0000967 AC: 4 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000679 Hom.: 1

Bravo AF: 0.0000453

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.27
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.37
MVP		0.55
MPC		0.0058
ClinPred		0.57	D
GERP RS		0.91
Varity_R		0.37
gMVP		0.52
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142020441; hg19: chr4-69796909; COSMIC: COSV52358923;