chr8-125024576-AT-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_014846.4(WASHC5):c.*40del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,405,236 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
WASHC5
NM_014846.4 3_prime_UTR
NM_014846.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.111
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.
BP6
Variant 8-125024576-AT-A is Benign according to our data. Variant chr8-125024576-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 361709.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000742 (113/152328) while in subpopulation AMR AF= 0.00111 (17/15304). AF 95% confidence interval is 0.000821. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.*40del | 3_prime_UTR_variant | 29/29 | ENST00000318410.12 | NP_055661.3 | ||
WASHC5 | NM_001330609.2 | c.*40del | 3_prime_UTR_variant | 28/28 | NP_001317538.1 | |||
WASHC5 | XM_047422502.1 | c.*40del | 3_prime_UTR_variant | 30/30 | XP_047278458.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.*40del | 3_prime_UTR_variant | 29/29 | 1 | NM_014846.4 | ENSP00000318016 | P1 | ||
WASHC5 | ENST00000517845.5 | c.*40del | 3_prime_UTR_variant | 27/27 | 2 | ENSP00000429676 | ||||
WASHC5 | ENST00000519042.2 | n.659del | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000742 AC: 113AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000921 AC: 230AN: 249816Hom.: 1 AF XY: 0.000852 AC XY: 115AN XY: 135030
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GnomAD4 exome AF: 0.00135 AC: 1691AN: 1252908Hom.: 3 Cov.: 19 AF XY: 0.00134 AC XY: 852AN XY: 634172
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GnomAD4 genome AF: 0.000742 AC: 113AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000765 AC XY: 57AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at