8-125044113-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The ENST00000318410.12(WASHC5):c.2668-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,486,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 1 hom. )
Consequence
WASHC5
ENST00000318410.12 intron
ENST00000318410.12 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.416
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 8-125044113-G-A is Benign according to our data. Variant chr8-125044113-G-A is described in ClinVar as [Benign]. Clinvar id is 1599873.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00051 (681/1334694) while in subpopulation NFE AF= 0.000637 (635/996900). AF 95% confidence interval is 0.000596. There are 1 homozygotes in gnomad4_exome. There are 300 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.2668-19C>T | intron_variant | ENST00000318410.12 | NP_055661.3 | |||
WASHC5-AS1 | NR_170219.1 | n.97-386G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2668-19C>T | intron_variant | 1 | NM_014846.4 | ENSP00000318016 | P1 | |||
WASHC5-AS1 | ENST00000519140.1 | n.97-386G>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
WASHC5 | ENST00000517845.5 | c.2224-19C>T | intron_variant | 2 | ENSP00000429676 |
Frequencies
GnomAD3 genomes AF: 0.000362 AC: 55AN: 152070Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000351 AC: 87AN: 247526Hom.: 0 AF XY: 0.000336 AC XY: 45AN XY: 134000
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GnomAD4 exome AF: 0.000510 AC: 681AN: 1334694Hom.: 1 Cov.: 20 AF XY: 0.000447 AC XY: 300AN XY: 670954
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GnomAD4 genome AF: 0.000361 AC: 55AN: 152188Hom.: 1 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74402
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ClinVar
Significance: 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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 05, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at