rs10865994

Positions:

• chr3-55466380-T-A
• chr3-55466380-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.*3712A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,000 control chromosomes in the GnomAD database, including 14,413 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 0.42 (14413 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.*3712A>T		3_prime_UTR_variant	5/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.*3712A>T		3_prime_UTR_variant	5/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.*3712A>T		3_prime_UTR_variant	6/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64524 AN: 151878 Hom.: 14407 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.425 AC: 64538 AN: 151998 Hom.: 14413 Cov.: 32 AF XY: 0.425 AC XY: 31563 AN XY: 74302

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.443

Alfa AF: 0.428 Hom.: 1871

Bravo AF: 0.436

Asia WGS AF: 0.493 AC: 1711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	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: rs10865994; hg19: chr3-55500408;