4-68930054-T-A

Position:

• chr4-68930054-T-A

Variant summary

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

The NM_024743.4(UGT2A3):​c.1343A>T​(p.His448Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.206

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]

UGT2A3 (HGNC:):

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	Protein	UniProt
UGT2A3	NM_024743.4	c.1343A>T	p.His448Leu	missense_variant	6/6	ENST00000251566.9	NP_079019.3
UGT2A3	XM_011532247.3	c.1361A>T	p.His454Leu	missense_variant	6/6		XP_011530549.1
UGT2A3	XM_047416177.1	c.476A>T	p.His159Leu	missense_variant	6/6		XP_047272133.1
UGT2A3	NR_024010.2	n.1484A>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2A3	ENST00000251566.9	c.1343A>T	p.His448Leu	missense_variant	6/6	1	NM_024743.4	ENSP00000251566.4
UGT2A3	ENST00000503012.1	n.*519A>T		non_coding_transcript_exon_variant	7/7	2		ENSP00000424092.1
UGT2A3	ENST00000503012.1	n.*519A>T		3_prime_UTR_variant	7/7	2		ENSP00000424092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.1343A>T (p.H448L) alteration is located in exon 6 (coding exon 6) of the UGT2A3 gene. This alteration results from a A to T substitution at nucleotide position 1343, causing the histidine (H) at amino acid position 448 to be replaced by a leucine (L). 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	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.085	N
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.61		Loss of disorder (P = 0.054);
MVP		0.42
MPC		0.018
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.54
gMVP		0.43

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.

Other links and lift over

hg19: chr4-69795772;