chr8-125043993-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_014846.4(WASHC5):c.2769C>T(p.Val923=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,609,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Consequence
NM_014846.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.2769C>T | p.Val923= | splice_region_variant, synonymous_variant | 22/29 | ENST00000318410.12 | |
WASHC5-AS1 | NR_170219.1 | n.97-506G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2769C>T | p.Val923= | splice_region_variant, synonymous_variant | 22/29 | 1 | NM_014846.4 | P1 | |
WASHC5-AS1 | ENST00000519140.1 | n.97-506G>A | intron_variant, non_coding_transcript_variant | 4 | |||||
WASHC5 | ENST00000517845.5 | c.2325C>T | p.Val775= | splice_region_variant, synonymous_variant | 20/27 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251346Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135840
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1457578Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 725472
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74396
ClinVar
Submissions by phenotype
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 01, 2018 | This sequence change affects codon 923 of the WASHC5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the WASHC5 protein. This variant is present in population databases (rs545318648, ExAC 0.02%). This variant has not been reported in the literature in individuals with WASHC5-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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