5-36039545-C-A

Variant summary

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

The NM_174914.4(UGT3A2):c.1007G>T(p.Trp336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT3A2 NM_174914.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

Genes affected

UGT3A2 (HGNC:27266): (UDP glycosyltransferase family 3 member A2) Enables UDP-glycosyltransferase activity. Acts upstream of or within cellular response to genistein. 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=0.18742156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT3A2	NM_174914.4	c.1007G>T	p.Trp336Leu	missense_variant	5/7	ENST00000282507.8
UGT3A2	NM_001168316.2	c.905G>T	p.Trp302Leu	missense_variant	4/6
UGT3A2	XM_011513988.2	c.1088G>T	p.Trp363Leu	missense_variant	6/8
UGT3A2	NR_031764.2	n.568G>T		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT3A2	ENST00000282507.8	c.1007G>T	p.Trp336Leu	missense_variant	5/7	1	NM_174914.4	P1
UGT3A2	ENST00000513300.5	c.905G>T	p.Trp302Leu	missense_variant	4/6	2
UGT3A2	ENST00000504685.5	c.*112G>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135916

Gnomad AFR exome AF: 0.0000615

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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

Jan 05, 2022

The c.1007G>T (p.W336L) alteration is located in exon 5 (coding exon 5) of the UGT3A2 gene. This alteration results from a G to T substitution at nucleotide position 1007, causing the tryptophan (W) at amino acid position 336 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	0.30
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	19
Dann	Benign	0.89
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.89	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.13
Sift	Benign	0.035	D;D
Sift4G	Uncertain	0.054	T;T
Polyphen		0.027	B;.
Vest4		0.31
MVP		0.36
MPC		0.13
ClinPred		0.43	T
GERP RS		2.4
Varity_R		0.27
gMVP		0.40

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: rs149684501; hg19: chr5-36039647;