11-76194756-G-T

Variant names:

• chr11-76194756-G-T
• rs1533767
• NM_004626.3:c.408C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004626.3(WNT11):​c.408C>A​(p.Pro136Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: WNT11 NM_004626.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT11	NM_004626.3	MANE Select	c.408C>A	p.Pro136Pro	synonymous	Exon 3 of 5	NP_004617.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT11	ENST00000322563.8	TSL:1 MANE Select	c.408C>A	p.Pro136Pro	synonymous	Exon 3 of 5	ENSP00000325526.3
	ENSG00000254933	ENST00000527314.1	TSL:4	n.298G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401758 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 691952

African (AFR) AF: 0.00 AC: 0 AN: 31910

American (AMR) AF: 0.00 AC: 0 AN: 36680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 36234

South Asian (SAS) AF: 0.00 AC: 0 AN: 79478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4242

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082102

Other (OTH) AF: 0.00 AC: 0 AN: 58046

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1533767; hg19: chr11-75905800;