rs1409607754

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_000377.3(WAS):c.1080A>C(p.Pro360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 0 hem., cov: 12)

Exomes 𝑓: 0.00042 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

WAS
NM_000377.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.0100

Variant links:

Genes affected

WAS (HGNC:12731): (WASP actin nucleation promoting factor) The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5' UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq, Jul 2008]

WAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-48688808-A-C is Benign according to our data. Variant chrX-48688808-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437265.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-0.01 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAS	NM_000377.3 linkuse as main transcript	c.1080A>C	p.Pro360=	synonymous_variant	10/12	ENST00000376701.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAS	ENST00000376701.5 linkuse as main transcript	c.1080A>C	p.Pro360=	synonymous_variant	10/12	1	NM_000377.3	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

50322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12600

FAILED QC

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00168

Gnomad ASJ

AF:

0.000803

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.00297

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00155

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000416

AC:

260

AN:

625176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

180036

show subpopulations

Gnomad4 AFR exome

AF:

0.000600

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.000914

Gnomad4 EAS exome

AF:

0.000924

Gnomad4 SAS exome

AF:

0.000368

Gnomad4 FIN exome

AF:

0.000941

Gnomad4 NFE exome

AF:

0.000323

Gnomad4 OTH exome

AF:

0.000773

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00161

AC:

AN:

50340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12606

show subpopulations

Gnomad4 AFR

AF:

0.00151

Gnomad4 AMR

AF:

0.00168

Gnomad4 ASJ

AF:

0.000803

Gnomad4 EAS

AF:

0.00180

Gnomad4 SAS

AF:

0.00298

Gnomad4 FIN

AF:

0.00329

Gnomad4 NFE

AF:

0.00155

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0506

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 09, 2016

- -

Wiskott-Aldrich syndrome;C1839163:Thrombocytopenia 1;C1845987:X-linked severe congenital neutropenia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

WAS: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

Cadd

Benign

9.3

Dann

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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