Variant 22-45923167-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP3PP5_ModerateBS2

The NM_058238.3(WNT7B):c.739C>T(p.Arg247Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

WNT7B
NM_058238.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.04

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 -1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

PP5

Variant 22-45923167-G-A is Pathogenic according to our data. Variant chr22-45923167-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 437886.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT7B	NM_058238.3 linkuse as main transcript	c.739C>T	p.Arg247Trp	missense_variant	4/4	ENST00000339464.9	NP_478679.1	P56706
WNT7B	NM_001410806.1 linkuse as main transcript	c.751C>T	p.Arg251Trp	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.739C>T	p.Arg247Trp	missense_variant	4/4	1	NM_058238.3	ENSP00000341032.4	P56706
WNT7B	ENST00000409496.7 linkuse as main transcript	c.751C>T	p.Arg251Trp	missense_variant	4/4	2		ENSP00000386546.3	A8K0G1
WNT7B	ENST00000410089.5 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	4/4	5		ENSP00000386781.1	B8A595

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461068

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726846

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anophthalmia-microphthalmia syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Paul Sabatier University EA-4555, Paul Sabatier University

Aug 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.92

D;.;D

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Uncertain

0.18

MutationAssessor

Pathogenic

3.2

M;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.56

MutPred

0.58

.;Loss of methylation at R251 (P = 0.0453);.;

MVP

0.94

MPC

1.8

ClinPred

0.99

GERP RS

2.7

Varity_R

0.40

gMVP

0.57

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