8-125024687-GAATTA-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_014846.4(WASHC5):c.3424-19_3424-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,567,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
WASHC5
NM_014846.4 splice_polypyrimidine_tract, intron
NM_014846.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.69
Genes affected
WASHC5 (HGNC:28984): (WASH complex subunit 5) This gene encodes a 134 kDa protein named strumpellin that is predicted to have multiple transmembrane domains and a spectrin-repeat-containing domain. This ubiquitously expressed gene has its highest expression in skeletal muscle. The protein is named for Strumpell disease; a form of hereditary spastic paraplegia (HSP). Spastic paraplegias are a diverse group of disorders in which the autosomal dominant forms are characterized by progressive, lower extremity spasticity caused by axonal degeneration in the terminal portions of the longest descending and ascending corticospinal tracts. More than 30 loci (SPG1-33) have been implicated in hereditary spastic paraplegia diseases. [provided by RefSeq, Aug 2009]
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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;
BP6
Variant 8-125024687-GAATTA-G is Benign according to our data. Variant chr8-125024687-GAATTA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1966591.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.3424-19_3424-15del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000318410.12 | NP_055661.3 | |||
WASHC5 | NM_001330609.2 | c.2980-19_2980-15del | splice_polypyrimidine_tract_variant, intron_variant | NP_001317538.1 | ||||
WASHC5 | XM_047422502.1 | c.3424-19_3424-15del | splice_polypyrimidine_tract_variant, intron_variant | XP_047278458.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.3424-19_3424-15del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014846.4 | ENSP00000318016 | P1 | |||
WASHC5 | ENST00000517845.5 | c.2980-19_2980-15del | splice_polypyrimidine_tract_variant, intron_variant | 2 | ENSP00000429676 | |||||
WASHC5 | ENST00000519042.2 | n.563-19_563-15del | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152036Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000600 AC: 15AN: 250128Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135302
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GnomAD4 exome AF: 0.0000502 AC: 71AN: 1415638Hom.: 0 AF XY: 0.0000636 AC XY: 45AN XY: 707048
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74240
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at