NM_000377.3:c.1188A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000377.3(WAS):​c.1188A>G​(p.Pro396Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000994 in 1,006,455 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P396P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.9e-7 ( 0 hom. 1 hem. )

Consequence

WAS
NM_000377.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • Wiskott-Aldrich syndrome
    Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
  • X-linked severe congenital neutropenia
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
  • thrombocytopenia 1
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP7
Synonymous conserved (PhyloP=-2.52 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WASNM_000377.3 linkc.1188A>G p.Pro396Pro synonymous_variant Exon 10 of 12 ENST00000376701.5 NP_000368.1 P42768A0A024QYX8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WASENST00000376701.5 linkc.1188A>G p.Pro396Pro synonymous_variant Exon 10 of 12 1 NM_000377.3 ENSP00000365891.4 P42768

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.94e-7
AC:
1
AN:
1006455
Hom.:
0
Cov.:
35
AF XY:
0.00000316
AC XY:
1
AN XY:
316531
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24095
American (AMR)
AF:
0.00
AC:
0
AN:
26606
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16297
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24804
South Asian (SAS)
AF:
0.00
AC:
0
AN:
46212
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
31173
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2967
European-Non Finnish (NFE)
AF:
0.00000126
AC:
1
AN:
792653
Other (OTH)
AF:
0.00
AC:
0
AN:
41648

Age Distribution

Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.20
DANN
Benign
0.28
PhyloP100
-2.5

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

Other links and lift over

dbSNP: rs1557007268; hg19: chrX-48547305; API