chr11-76187168-T-C

Position:

• chr11-76187168-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004626.3(WNT11):​c.962A>G​(p.Tyr321Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT11 NM_004626.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77

Genes affected

WNT11 (HGNC:12776): (Wnt family member 11) 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 encodes a protein which shows 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT11	NM_004626.3	c.962A>G	p.Tyr321Cys	missense_variant	5/5	ENST00000322563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT11	ENST00000322563.8	c.962A>G	p.Tyr321Cys	missense_variant	5/5	1	NM_004626.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 08, 2024

The c.962A>G (p.Y321C) alteration is located in exon 5 (coding exon 5) of the WNT11 gene. This alteration results from a A to G substitution at nucleotide position 962, causing the tyrosine (Y) at amino acid position 321 to be replaced by a cysteine (C). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.92	D;D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Pathogenic	0.69
Sift	Benign	0.14	T;.
Sift4G	Benign	0.12	T;T
Polyphen		1.0	D;.
Vest4		0.80
MutPred		0.50		Gain of disorder (P = 0.0323);.;
MVP		0.97
MPC		1.2
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.74
gMVP		0.68

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: chr11-75898212; COSMIC: COSV59443120; COSMIC: COSV59443120;