rs557077

Positions:

• chr3-55497239-G-A
• chr3-55497239-G-C

Variant summary

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

The XM_011534086.3(WNT5A):​c.-482+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,188 control chromosomes in the GnomAD database, including 12,422 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 0.35 (12419 hom., cov: 33)
  • Exomes 𝑓: 0.35 (3 hom.)
• Consequence: WNT5A XM_011534086.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

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]

ENSG00000242317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	XM_011534086.3	c.-482+150C>T		intron_variant			XP_011532388.1
WNT5A	XM_017007128.2	c.-487+150C>T		intron_variant			XP_016862617.1
WNT5A	XM_047448853.1	c.-3984+150C>T		intron_variant			XP_047304809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000242317	ENST00000472238.1	n.337+150C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52785 AN: 152044 Hom.: 12405 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.346 AC: 9 AN: 26 Hom.: 3 AF XY: 0.444 AC XY: 8 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.347 AC: 52835 AN: 152162 Hom.: 12419 Cov.: 33 AF XY: 0.346 AC XY: 25739 AN XY: 74376

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.308

Alfa AF: 0.232 Hom.: 7053

Bravo AF: 0.366

Asia WGS AF: 0.261 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs557077; hg19: chr3-55531267;