rs148800063

Positions:

chrX-48683943-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000377.3(WAS):c.90C>T(p.His30His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,209,192 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 388 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., 16 hem., cov: 22)

Exomes 𝑓: 0.0010 ( 0 hom. 372 hem. )

Consequence

WAS
NM_000377.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.85

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:

WAS (HGNC:):

WAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-48683943-C-T is Benign according to our data. Variant chrX-48683943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 458506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-48683943-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000586 (65/110945) while in subpopulation SAS AF= 0.00114 (3/2639). AF 95% confidence interval is 0.000854. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAS	NM_000377.3 linkuse as main transcript	c.90C>T	p.His30His	synonymous_variant	1/12	ENST00000376701.5	NP_000368.1	P42768A0A024QYX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WAS	ENST00000376701.5 linkuse as main transcript	c.90C>T	p.His30His	synonymous_variant	1/12	1	NM_000377.3	ENSP00000365891.4		P42768

Frequencies

GnomAD3 genomes

AF:

0.000586

AC:

AN:

110945

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

33103

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000956

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00108

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000714

AC:

131

AN:

183418

Hom.:

AF XY:

0.000855

AC XY:

AN XY:

67856

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000891

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.00101

AC:

1106

AN:

1098247

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

372

AN XY:

363603

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000572

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000824

GnomAD4 genome

AF:

0.000586

AC:

AN:

110945

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

33103

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00108

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000582

Hom.:

Bravo

AF:

0.000567

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 26, 2018

- -

WAS-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.4

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