Variant chr3-55474616-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.10

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.405G>T	p.Thr135=	synonymous_variant	4/5	1	NM_003392.7	P1	P41221-1
WNT5A	ENST00000474267.5 linkuse as main transcript	c.405G>T	p.Thr135=	synonymous_variant	5/6	5		P1	P41221-1
WNT5A	ENST00000497027.5 linkuse as main transcript	c.360G>T	p.Thr120=	synonymous_variant	4/5	2			P41221-2
WNT5A	ENST00000482079.1 linkuse as main transcript	c.360G>T	p.Thr120=	synonymous_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4023

AN:

144424

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0298

AC XY:

843

AN XY:

28302

show subpopulations

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.:

AF XY:

0.0447

AC XY:

27115

AN XY:

606386

show subpopulations

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.:

Cov.:

AF XY:

0.0259

AC XY:

1818

AN XY:

70240

show subpopulations

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.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.0100

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over