3-55474616-C-G

Variant names:

• chr3-55474616-C-G
• rs147104982
• NM_003392.7:c.405G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003392.7(WNT5A):​c.405G>C​(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 144,538 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. Synonymous variant affecting the same amino acid position (i.e. T135T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 1 publications found

Genes affected

WNT5A (HGNC:12784): (Wnt family member 5A) 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 encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

WNT5A Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	NM_003392.7	MANE Select	c.405G>C	p.Thr135Thr	synonymous	Exon 4 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.360G>C	p.Thr120Thr	synonymous	Exon 4 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.360G>C	p.Thr120Thr	synonymous	Exon 4 of 5	NP_001364200.1	P41221-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.405G>C	p.Thr135Thr	synonymous	Exon 4 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.405G>C	p.Thr135Thr	synonymous	Exon 5 of 6	ENSP00000417310.1	P41221-1
	WNT5A	ENST00000497027.5	TSL:2	c.360G>C	p.Thr120Thr	synonymous	Exon 4 of 5	ENSP00000420104.1	P41221-2

Frequencies

GnomAD3 genomes AF: 0.0000208 AC: 3 AN: 144442 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000453

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1250634 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 606410

African (AFR) AF: 0.00 AC: 0 AN: 25390

American (AMR) AF: 0.00 AC: 0 AN: 18860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17218

East Asian (EAS) AF: 0.00 AC: 0 AN: 30732

South Asian (SAS) AF: 0.00 AC: 0 AN: 61434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3942

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1009044

Other (OTH) AF: 0.00 AC: 0 AN: 50742

GnomAD4 genome AF: 0.0000208 AC: 3 AN: 144538 Hom.: 0 Cov.: 28 AF XY: 0.0000285 AC XY: 2 AN XY: 70246

African (AFR) AF: 0.00 AC: 0 AN: 38956

American (AMR) AF: 0.00 AC: 0 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4548

South Asian (SAS) AF: 0.00 AC: 0 AN: 4198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000454 AC: 3 AN: 66142

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.0000393 Hom.: 74

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.5
DANN	Benign	0.85
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs147104982; hg19: chr3-55508644;