rs797044477

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000376701.5(WAS):​c.58C>G​(p.Gln20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

WAS
ENST00000376701.5 missense

Scores

1
5
11

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19102383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASNM_000377.3 linkuse as main transcriptc.58C>G p.Gln20Glu missense_variant 1/12 ENST00000376701.5 NP_000368.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WASENST00000376701.5 linkuse as main transcriptc.58C>G p.Gln20Glu missense_variant 1/121 NM_000377.3 ENSP00000365891 P2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
22

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
17
DANN
Benign
0.67
DEOGEN2
Benign
0.0022
T;T
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.65
T;T
M_CAP
Pathogenic
0.86
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Uncertain
0.47
D
MutationAssessor
Benign
1.5
.;L
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.12
N;N
REVEL
Uncertain
0.43
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.032
.;B
Vest4
0.23
MutPred
0.14
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.88
MPC
0.64
ClinPred
0.14
T
GERP RS
4.3
Varity_R
0.13
gMVP
0.67

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.

Other links and lift over

dbSNP: rs797044477; hg19: chrX-48542300; API