rs72720524
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_014846.4(WASHC5):c.647C>T(p.Pro216Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,926 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014846.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.647C>T | p.Pro216Leu | missense_variant | Exon 6 of 29 | 1 | NM_014846.4 | ENSP00000318016.7 | ||
WASHC5 | ENST00000517845.5 | c.203C>T | p.Pro68Leu | missense_variant | Exon 4 of 27 | 2 | ENSP00000429676.1 | |||
WASHC5 | ENST00000523297.5 | c.203C>T | p.Pro68Leu | missense_variant | Exon 5 of 7 | 3 | ENSP00000427946.1 |
Frequencies
GnomAD3 genomes AF: 0.000934 AC: 142AN: 152082Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00108 AC: 272AN: 251368Hom.: 0 AF XY: 0.00111 AC XY: 151AN XY: 135848
GnomAD4 exome AF: 0.00113 AC: 1654AN: 1461726Hom.: 2 Cov.: 31 AF XY: 0.00109 AC XY: 791AN XY: 727172
GnomAD4 genome AF: 0.000933 AC: 142AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.000981 AC XY: 73AN XY: 74408
ClinVar
Submissions by phenotype
not provided Uncertain:3
PP3 -
A variant of uncertain significance has been identified in the KIAA0196 gene. The P216L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P216L variant is observed in 29/6612 (0.4%) alleles from individuals of European Finnish background and in 113/66722 (0.2%) alleles from individuals of European non-Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P216L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
WASHC5: PP3 -
Hereditary spastic paraplegia 8 Benign:1
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
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Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at