chr4-68930619-C-G

Variant names:

• chr4-68930619-C-G
• rs1432463055
• NM_024743.4:c.1231G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024743.4(UGT2A3):​c.1231G>C​(p.Val411Leu) 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 1,461,394 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1333563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2A3	NM_024743.4	c.1231G>C	p.Val411Leu	missense_variant	Exon 5 of 6	ENST00000251566.9	NP_079019.3
UGT2A3	XM_011532247.3	c.1249G>C	p.Val417Leu	missense_variant	Exon 5 of 6		XP_011530549.1
UGT2A3	XM_047416177.1	c.364G>C	p.Val122Leu	missense_variant	Exon 5 of 6		XP_047272133.1
UGT2A3	NR_024010.2	n.1372G>C		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2A3	ENST00000251566.9	c.1231G>C	p.Val411Leu	missense_variant	Exon 5 of 6	1	NM_024743.4	ENSP00000251566.4
UGT2A3	ENST00000503012.1	n.*407G>C		non_coding_transcript_exon_variant	Exon 6 of 7	2		ENSP00000424092.1
UGT2A3	ENST00000503012.1	n.*407G>C		3_prime_UTR_variant	Exon 6 of 7	2		ENSP00000424092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250982 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135668

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461394 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727004

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.027
Sift	Benign	0.049	D
Sift4G	Benign	0.084	T
Polyphen		0.10	B
Vest4		0.12
MutPred		0.68		Loss of methylation at K416 (P = 0.0779);
MVP		0.16
MPC		0.0069
ClinPred		0.083	T
GERP RS		-0.093
Varity_R		0.090
gMVP		0.21

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: rs1432463055; hg19: chr4-69796337;