rs6596422

chr5-138090758-G-Achr5-138090758-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001300939.2(WNT8A):c.795G>A(p.Ala265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,613,938 control chromosomes in the GnomAD database, including 180,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15206 hom., cov: 32)
  • Exomes 𝑓: 0.47 (165780 hom.)
• Consequence: WNT8A NM_001300939.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT8A	NM_001300939.2	c.795G>A	p.Ala265=	synonymous_variant	5/5	ENST00000506684.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT8A	ENST00000506684.6	c.795G>A	p.Ala265=	synonymous_variant	5/5	1	NM_001300939.2
WNT8A	ENST00000504809.5	c.795G>A	p.Ala265=	synonymous_variant	5/6	1
WNT8A	ENST00000398754.1	c.741G>A	p.Ala247=	synonymous_variant	6/6	1		P1
WNT8A	ENST00000361560.6	c.741G>A	p.Ala247=	synonymous_variant, NMD_transcript_variant	6/8	1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66593 AN: 151958 Hom.: 15205 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.469

GnomAD3 exomes AF: 0.479 AC: 119406 AN: 249230 Hom.: 29050 AF XY: 0.483 AC XY: 65346 AN XY: 135264

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.589

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.474 AC: 692667 AN: 1461862 Hom.: 165780 Cov.: 76 AF XY: 0.476 AC XY: 345867 AN XY: 727234

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.438 AC: 66621 AN: 152076 Hom.: 15206 Cov.: 32 AF XY: 0.442 AC XY: 32841 AN XY: 74326

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.473

Alfa AF: 0.467 Hom.: 11621

Bravo AF: 0.433

Asia WGS AF: 0.562 AC: 1958 AN: 3478

EpiCase AF: 0.489

EpiControl AF: 0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.44
Dann	Benign	0.55

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: rs6596422; hg19: chr5-137426447; COSMIC: COSV64230906;