7-121329754-A-T

Position:

• chr7-121329754-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_057168.2(WNT16):​c.283A>T​(p.Thr95Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.57

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047101557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT16	NM_057168.2	c.283A>T	p.Thr95Ser	missense_variant	2/4	ENST00000222462.3	NP_476509.1
WNT16	NM_016087.2	c.253A>T	p.Thr85Ser	missense_variant	2/4		NP_057171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3	c.283A>T	p.Thr95Ser	missense_variant	2/4	1	NM_057168.2	ENSP00000222462.2
WNT16	ENST00000361301.6	c.253A>T	p.Thr85Ser	missense_variant	2/4	1		ENSP00000355065.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.283A>T (p.T95S) alteration is located in exon 2 (coding exon 2) of the WNT16 gene. This alteration results from a A to T substitution at nucleotide position 283, causing the threonine (T) at amino acid position 95 to be replaced by a serine (S). 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	0.064
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.37
DANN	Benign	0.64
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.22	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.65	.;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.30	N;N
REVEL	Benign	0.11
Sift	Benign	0.71	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0	B;B
Vest4		0.068
MutPred		0.47		.;Gain of glycosylation at T95 (P = 0.1232);
MVP		0.52
MPC		0.14
ClinPred		0.055	T
GERP RS		1.6
Varity_R		0.066
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-120969808;