8-125043911-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014846.4(WASHC5):c.2771-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,610,748 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_014846.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.2771-7T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000318410.12 | NP_055661.3 | |||
WASHC5-AS1 | NR_170219.1 | n.97-588A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2771-7T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014846.4 | ENSP00000318016 | P1 | |||
WASHC5-AS1 | ENST00000519140.1 | n.97-588A>G | intron_variant, non_coding_transcript_variant | 4 | ||||||
WASHC5 | ENST00000517845.5 | c.2327-7T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | ENSP00000429676 |
Frequencies
GnomAD3 genomes AF: 0.00165 AC: 251AN: 152208Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000446 AC: 112AN: 251050Hom.: 1 AF XY: 0.000309 AC XY: 42AN XY: 135714
GnomAD4 exome AF: 0.000197 AC: 287AN: 1458422Hom.: 2 Cov.: 29 AF XY: 0.000189 AC XY: 137AN XY: 725842
GnomAD4 genome AF: 0.00165 AC: 251AN: 152326Hom.: 1 Cov.: 33 AF XY: 0.00158 AC XY: 118AN XY: 74494
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 05, 2014 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 02, 2021 | - - |
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 05, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at