Variant 1-68144577-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024911.7(WLS):c.1354G>A(p.Val452Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

WLS
NM_024911.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

WLS (HGNC:30238): (Wnt ligand secretion mediator) Enables Wnt-protein binding activity and identical protein binding activity. Involved in positive regulation of cell communication and protein transport. Located in several cellular components, including Golgi apparatus; early endosome; and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

WLS links:

GNG12-AS1 (HGNC:43938): (GNG12, DIRAS3 and WLS antisense RNA 1)

GNG12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15898177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WLS	NM_024911.7 linkuse as main transcript	c.1354G>A	p.Val452Ile	missense_variant	10/12	ENST00000262348.9
GNG12-AS1	NR_040077.1 linkuse as main transcript	n.1228+6127C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WLS	ENST00000262348.9 linkuse as main transcript	c.1354G>A	p.Val452Ile	missense_variant	10/12	1	NM_024911.7	P1	Q5T9L3-1
GNG12-AS1	ENST00000420587.5 linkuse as main transcript	n.1213+6127C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251294

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.1348G>A (p.V450I) alteration is located in exon 10 (coding exon 10) of the WLS gene. This alteration results from a G to A substitution at nucleotide position 1348, causing the valine (V) at amino acid position 450 to be replaced by an isoleucine (I). 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

0.078

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.064

.;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.40

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.029

B;B;.

Vest4

0.20

MutPred

0.33

.;Loss of catalytic residue at V452 (P = 0.0152);.;

MVP

0.27

MPC

0.15

ClinPred

0.26

GERP RS

5.6

Varity_R

0.051

gMVP

0.20

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over