11-76191700-T-C

Variant names:

• chr11-76191700-T-C
• rs767000407
• NM_004626.3:c.754A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004626.3(WNT11):​c.754A>G​(p.Met252Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WNT11 NM_004626.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38038105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT11	NM_004626.3	c.754A>G	p.Met252Val	missense_variant	Exon 4 of 5	ENST00000322563.8	NP_004617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT11	ENST00000322563.8	c.754A>G	p.Met252Val	missense_variant	Exon 4 of 5	1	NM_004626.3	ENSP00000325526.3
ENSG00000254933	ENST00000527314.1	n.182+794T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727148

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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	Benign	0.062
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
DANN	Benign	0.77
DEOGEN2	Benign	0.42	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.18	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.52	N;.
REVEL	Uncertain	0.34
Sift	Benign	1.0	T;.
Sift4G	Benign	0.85	T;T
Polyphen		0.010	B;.
Vest4		0.64
MutPred		0.37		Loss of catalytic residue at V248 (P = 0.0221);.;
MVP		0.77
MPC		0.42
ClinPred		0.18	T
GERP RS		5.7
Varity_R		0.20
gMVP		0.47

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: rs767000407; hg19: chr11-75902744;