Variant 22-45931237-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_058238.3(WNT7B):c.431C>A(p.Ala144Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000498 in 1,599,174 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: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

WNT7B
NM_058238.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07030183).

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT7B	NM_058238.3 linkuse as main transcript	c.431C>A	p.Ala144Asp	missense_variant	3/4	ENST00000339464.9	NP_478679.1	P56706
WNT7B	NM_001410806.1 linkuse as main transcript	c.443C>A	p.Ala148Asp	missense_variant	3/4		NP_001397735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WNT7B	ENST00000339464.9 linkuse as main transcript	c.431C>A	p.Ala144Asp	missense_variant	3/4	1	NM_058238.3	ENSP00000341032.4	P56706
WNT7B	ENST00000409496.7 linkuse as main transcript	c.443C>A	p.Ala148Asp	missense_variant	3/4	2		ENSP00000386546.3	A8K0G1
WNT7B	ENST00000410089.5 linkuse as main transcript	c.383C>A	p.Ala128Asp	missense_variant	3/4	5		ENSP00000386781.1	B8A595
WNT7B	ENST00000410058.1 linkuse as main transcript	c.431C>A	p.Ala144Asp	missense_variant	3/4	3		ENSP00000387217.1	B8A597

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000209

AC:

AN:

239708

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

130886

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:

0.000437

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000522

AC:

755

AN:

1446936

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

357

AN XY:

720380

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000258

Gnomad4 NFE exome

AF:

0.000664

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000269

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

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

Oct 26, 2021

The c.431C>A (p.A144D) alteration is located in exon 3 (coding exon 3) of the WNT7B gene. This alteration results from a C to A substitution at nucleotide position 431, causing the alanine (A) at amino acid position 144 to be replaced by an aspartic acid (D). 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

0.086

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Uncertain

0.44

T;.;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.070

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.55

N;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.23

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.65

T;T;T;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.41

MVP

0.62

MPC

1.1

ClinPred

0.071

GERP RS

0.78

Varity_R

0.14

gMVP

0.39

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