Genetic Variant WNT8A:n.*462T>G (chr5-138092398-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000361560.6(WNT8A):n.*462T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,096 control chromosomes in the GnomAD database, including 15,160 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 ( 15160 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

WNT8A
ENST00000361560.6 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.623

Variant links:

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]

WNT8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8A	NR_125351.2 link	n.*33T>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8A	ENST00000361560.6 link	n.*462T>G		downstream_gene_variant		1		ENSP00000354726.2		Q9H1J5-2

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66489

AN:

151978

Hom.:

15159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.467

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.437

AC:

66515

AN:

152096

Hom.:

15160

Cov.:

AF XY:

0.441

AC XY:

32789

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.604

Gnomad4 SAS

AF:

0.504

Gnomad4 FIN

AF:

0.468

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.470

Alfa

AF:

0.467

Hom.:

5195

Bravo

AF:

0.432

Asia WGS

AF:

0.561

AC:

1953

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over