Variant 22-45931177-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_058238.3(WNT7B):c.491G>A(p.Arg164Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,447,198 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

WNT7B
NM_058238.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT7B	NM_058238.3 linkuse as main transcript	c.491G>A	p.Arg164Gln	missense_variant	3/4	ENST00000339464.9
WNT7B	NM_001410806.1 linkuse as main transcript	c.503G>A	p.Arg168Gln	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WNT7B	ENST00000339464.9 linkuse as main transcript	c.491G>A	p.Arg164Gln	missense_variant	3/4	1	NM_058238.3	P4
WNT7B	ENST00000409496.7 linkuse as main transcript	c.503G>A	p.Arg168Gln	missense_variant	3/4	2		A1
WNT7B	ENST00000410089.5 linkuse as main transcript	c.443G>A	p.Arg148Gln	missense_variant	3/4	5
WNT7B	ENST00000410058.1 linkuse as main transcript	c.491G>A	p.Arg164Gln	missense_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1447198

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Dec 13, 2021

The c.491G>A (p.R164Q) alteration is located in exon 3 (coding exon 3) of the WNT7B gene. This alteration results from a G to A substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;.;D;.

Eigen

Benign

0.064

Eigen_PC

Benign

0.064

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

2.0

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.075

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.67

P;P;.;.

Vest4

0.75

MutPred

0.77

.;Loss of MoRF binding (P = 0.0252);.;.;

MVP

0.89

MPC

1.1

ClinPred

0.98

GERP RS

2.1

Varity_R

0.34

gMVP

0.76

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