rs12497254

Variant names:

• chr3-55465636-G-A
• rs12497254
• NM_003392.7:c.*4456C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-55465636-G-A
• chr3-55465636-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003392.7(WNT5A):​c.*4456C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,964 control chromosomes in the GnomAD database, including 15,132 homozygotes. 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: 𝑓 0.44 (15132 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*4456C>T		downstream_gene_variant		ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.*4456C>T		downstream_gene_variant		1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5	c.*4456C>T		downstream_gene_variant		5		ENSP00000417310.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66570 AN: 151846 Hom.: 15125 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66585 AN: 151964 Hom.: 15132 Cov.: 32 AF XY: 0.438 AC XY: 32547 AN XY: 74260

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.454

Alfa AF: 0.456 Hom.: 16044

Bravo AF: 0.451

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12497254; hg19: chr3-55499664;