3-55467147-T-C

Variant summary

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

The NM_003392.7(WNT5A):c.*2945A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,998 control chromosomes in the GnomAD database, including 14,763 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 0.43 (14761 hom., cov: 32)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.*2945A>G		3_prime_UTR_variant	5/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.*2945A>G		3_prime_UTR_variant	5/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.*2945A>G		3_prime_UTR_variant	6/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65472 AN: 151828 Hom.: 14756 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.385 AC: 20 AN: 52 Hom.: 2 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

Gnomad4 FIN exome AF: 0.385

GnomAD4 genome AF: 0.431 AC: 65484 AN: 151946 Hom.: 14761 Cov.: 32 AF XY: 0.431 AC XY: 32026 AN XY: 74292

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.445

Alfa AF: 0.456 Hom.: 15868

Bravo AF: 0.443

Asia WGS AF: 0.492 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.1
Dann	Benign	0.83

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: rs1829556; hg19: chr3-55501175;