Variant 7-121329754-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_057168.2(WNT16):c.283A>G(p.Thr95Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WNT16
NM_057168.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.57

Variant links:

Genes affected

WNT16 (HGNC:16267): (Wnt family member 16) The WNT gene family consists of structurally related genes which 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. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

WNT16 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047352105).

BP6

Variant 7-121329754-A-G is Benign according to our data. Variant chr7-121329754-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2620438.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT16	NM_057168.2 linkuse as main transcript	c.283A>G	p.Thr95Ala	missense_variant	2/4	ENST00000222462.3	NP_476509.1
WNT16	NM_016087.2 linkuse as main transcript	c.253A>G	p.Thr85Ala	missense_variant	2/4		NP_057171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3 linkuse as main transcript	c.283A>G	p.Thr95Ala	missense_variant	2/4	1	NM_057168.2	ENSP00000222462	P1	Q9UBV4-1
WNT16	ENST00000361301.6 linkuse as main transcript	c.253A>G	p.Thr85Ala	missense_variant	2/4	1		ENSP00000355065

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000425

AC:

AN:

235100

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

128978

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:

0.00000927

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452184

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722424

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.6

DANN

Benign

0.50

DEOGEN2

Benign

0.37

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.040

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.053

Sift

Benign

0.76

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.0

B;B

Vest4

0.048

MutPred

0.39

.;Loss of glycosylation at T95 (P = 0.0801);

MVP

0.53

MPC

0.15

ClinPred

0.025

GERP RS

1.6

Varity_R

0.056

gMVP

0.29

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