rs147104982

chr3-55474616-C-Achr3-55474616-C-Gchr3-55474616-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003392.7(WNT5A):c.405G>T(p.Thr135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,395,110 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (83 hom., cov: 28)
  • Exomes 𝑓: 0.046 (1481 hom.)
• Consequence: WNT5A NM_003392.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.10

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 3-55474616-C-A is Benign according to our data. Variant chr3-55474616-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 160315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.405G>T	p.Thr135=	synonymous_variant	4/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.405G>T	p.Thr135=	synonymous_variant	4/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.405G>T	p.Thr135=	synonymous_variant	5/6	5		P1
WNT5A	ENST00000497027.5	c.360G>T	p.Thr120=	synonymous_variant	4/5	2
WNT5A	ENST00000482079.1	c.360G>T	p.Thr120=	synonymous_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4023 AN: 144424 Hom.: 83 Cov.: 28

Gnomad AFR AF: 0.00844

Gnomad AMI AF: 0.00451

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00817

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0289

GnomAD3 exomes AF: 0.0291 AC: 1589 AN: 54660 Hom.: 30 AF XY: 0.0298 AC XY: 843 AN XY: 28302

Gnomad AFR exome AF: 0.00858

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0255

Gnomad FIN exome AF: 0.0236

Gnomad NFE exome AF: 0.0481

Gnomad OTH exome AF: 0.0323

GnomAD4 exome AF: 0.0456 AC: 57013 AN: 1250590 Hom.: 1481 Cov.: 33 AF XY: 0.0447 AC XY: 27115 AN XY: 606386

Gnomad4 AFR exome AF: 0.00614

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.0000976

Gnomad4 SAS exome AF: 0.0234

Gnomad4 FIN exome AF: 0.0261

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0405

GnomAD4 genome AF: 0.0278 AC: 4020 AN: 144520 Hom.: 83 Cov.: 28 AF XY: 0.0259 AC XY: 1818 AN XY: 70240

Gnomad4 AFR AF: 0.00842

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00817

Gnomad4 EAS AF: 0.000220

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0287

Alfa AF: 0.0322 Hom.: 38

Bravo AF: 0.0267

Asia WGS AF: 0.0100 AC: 36 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 07, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	7.3
Dann	Benign	0.93

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: rs147104982; hg19: chr3-55508644;