chr3-55466380-T-A

Variant names:

• chr3-55466380-T-A
• rs10865994
• NM_003392.7:c.*3712A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264634.9(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 ENST00000264634.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 21 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal dominant Robinow syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264634.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	NM_003392.7	MANE Select	c.*3712A>T		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*3712A>T		3_prime_UTR	Exon 5 of 5	NP_001243034.1
	WNT5A	NM_001377271.1		c.*3712A>T		3_prime_UTR	Exon 5 of 5	NP_001364200.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.*3712A>T		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4
	WNT5A	ENST00000474267.5	TSL:5	c.*3712A>T		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.313 AC: 12960 AN: 41450

American (AMR) AF: 0.563 AC: 8593 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3471 AN: 5168

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4820

European-Finnish (FIN) AF: 0.399 AC: 4210 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30473 AN: 67954

Other (OTH) AF: 0.443 AC: 934 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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: rs10865994; hg19: chr3-55500408;