NM_004626.3:c.383G>C

Variant names:

• chr11-76194781-C-G
• rs769163509
• NM_004626.3:c.383G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004626.3(WNT11):​c.383G>C​(p.Arg128Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WNT11 NM_004626.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99

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]

ENSG00000254933 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT11	NM_004626.3	c.383G>C	p.Arg128Pro	missense_variant	Exon 3 of 5	ENST00000322563.8	NP_004617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT11	ENST00000322563.8	c.383G>C	p.Arg128Pro	missense_variant	Exon 3 of 5	1	NM_004626.3	ENSP00000325526.3
ENSG00000254933	ENST00000527314.1	n.323C>G		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D;D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Pathogenic	3.7	H;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.6	D;.
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;.
Vest4		0.90
MutPred		0.84		Gain of glycosylation at T131 (P = 0.0299);Gain of glycosylation at T131 (P = 0.0299);
MVP		0.97
MPC		1.2
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.97
gMVP		0.98

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

Other links and lift over

dbSNP: rs769163509; hg19: chr11-75905825;