chrX-48683859-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000377.3(WAS):c.6T>C(p.Ser2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,955 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )
Consequence
WAS
NM_000377.3 synonymous
NM_000377.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.957
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant X-48683859-T-C is Benign according to our data. Variant chrX-48683859-T-C is described in ClinVar as [Benign]. Clinvar id is 2925814.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.957 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WAS | NM_000377.3 | c.6T>C | p.Ser2= | synonymous_variant | 1/12 | ENST00000376701.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WAS | ENST00000376701.5 | c.6T>C | p.Ser2= | synonymous_variant | 1/12 | 1 | NM_000377.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
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22
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 182601Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67125
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GnomAD4 exome AF: 0.00000729 AC: 8AN: 1097955Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 3AN XY: 363333
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GnomAD4 genome ? Cov.: 22
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wiskott-Aldrich syndrome;C1839163:Thrombocytopenia 1;C1845987:X-linked severe congenital neutropenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at