rs763639768
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014846.4(WASHC5):c.2003G>T(p.Gly668Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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.2003G>T | p.Gly668Val | missense_variant | 16/29 | ENST00000318410.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2003G>T | p.Gly668Val | missense_variant | 16/29 | 1 | NM_014846.4 | P1 | |
WASHC5 | ENST00000517845.5 | c.1559G>T | p.Gly520Val | missense_variant | 14/27 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461824Hom.: 1 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727216
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 02, 2022 | The c.2003G>T (p.G668V) alteration is located in exon 16 (coding exon 15) of the WASHC5 gene. This alteration results from a G to T substitution at nucleotide position 2003, causing the glycine (G) at amino acid position 668 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2018 | This variant has not been reported in the literature in individuals with WASHC5-related disease. This variant is present in population databases (rs763639768, ExAC 0.001%). This sequence change replaces glycine with valine at codon 668 of the WASHC5 protein (p.Gly668Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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