5-138087880-A-G

Variant names:

• chr5-138087880-A-G
• NM_001300939.2:c.370A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300939.2(WNT8A):​c.370A>G​(p.Met124Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT8A NM_001300939.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

WNT8A (HGNC:12788): (Wnt family member 8A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family, and may be implicated in development of early embryos as well as germ cell tumors. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.412817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8A	NM_001300939.2	c.370A>G	p.Met124Val	missense_variant	Exon 3 of 5	ENST00000506684.6	NP_001287868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8A	ENST00000506684.6	c.370A>G	p.Met124Val	missense_variant	Exon 3 of 5	1	NM_001300939.2	ENSP00000426653.1
WNT8A	ENST00000504809.5	c.370A>G	p.Met124Val	missense_variant	Exon 3 of 6	1		ENSP00000424809.1
WNT8A	ENST00000398754.1	c.316A>G	p.Met106Val	missense_variant	Exon 4 of 6	1		ENSP00000381739.1
WNT8A	ENST00000361560.6	n.316A>G		non_coding_transcript_exon_variant	Exon 4 of 8	1		ENSP00000354726.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316A>G (p.M106V) alteration is located in exon 4 (coding exon 4) of the WNT8A gene. This alteration results from a A to G substitution at nucleotide position 316, causing the methionine (M) at amino acid position 106 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.68	.;.;D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	.;.;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.10	T;T;D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.42	B;B;P
Vest4		0.51
MutPred		0.44		Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP		0.32
MPC		0.90
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137423569;