rs1554591077
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014846.4(WASHC5):āc.2971A>Gā(p.Ile991Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I991T) has been classified as Uncertain significance.
Frequency
Consequence
NM_014846.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.2971A>G | p.Ile991Val | missense_variant | 25/29 | ENST00000318410.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2971A>G | p.Ile991Val | missense_variant | 25/29 | 1 | NM_014846.4 | P1 | |
WASHC5 | ENST00000517845.5 | c.2527A>G | p.Ile843Val | missense_variant | 23/27 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461614Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727124
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces isoleucine with valine at codon 991 of the WASHC5 protein (p.Ile991Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with WASHC5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at