Variant chr22-45923047-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_058238.3(WNT7B):c.859G>A(p.Val287Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

WNT7B
NM_058238.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

WNT7B (HGNC:12787): (Wnt family member 7B) This gene is a member of the WNT gene family, which consists of structurally related genes that 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. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008]

WNT7B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3343794).

BS2

High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT7B	NM_058238.3 linkuse as main transcript	c.859G>A	p.Val287Met	missense_variant	4/4	ENST00000339464.9	NP_478679.1	P56706
WNT7B	NM_001410806.1 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	4/4		NP_001397735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WNT7B	ENST00000339464.9 linkuse as main transcript	c.859G>A	p.Val287Met	missense_variant	4/4	1	NM_058238.3	ENSP00000341032.4	P56706
WNT7B	ENST00000409496.7 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant	4/4	2		ENSP00000386546.3	A8K0G1
WNT7B	ENST00000410089.5 linkuse as main transcript	c.811G>A	p.Val271Met	missense_variant	4/4	5		ENSP00000386781.1	B8A595

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250240

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1460412

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Jan 17, 2024

The c.859G>A (p.V287M) alteration is located in exon 4 (coding exon 4) of the WNT7B gene. This alteration results from a G to A substitution at nucleotide position 859, causing the valine (V) at amino acid position 287 to be replaced by a methionine (M). 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

0.087

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.14

N;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.61

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.082

T;T;T

Polyphen

0.25

B;B;.

Vest4

0.15

MutPred

0.52

.;Gain of disorder (P = 0.0481);.;

MVP

0.73

MPC

0.80

ClinPred

0.13

GERP RS

3.9

Varity_R

0.15

gMVP

0.25

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