rs142883794
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014846.4(WASHC5):āc.2972T>Cā(p.Ile991Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I991M) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WASHC5 | NM_014846.4 | c.2972T>C | p.Ile991Thr | missense_variant | 25/29 | ENST00000318410.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WASHC5 | ENST00000318410.12 | c.2972T>C | p.Ile991Thr | missense_variant | 25/29 | 1 | NM_014846.4 | P1 | |
WASHC5 | ENST00000517845.5 | c.2528T>C | p.Ile843Thr | missense_variant | 23/27 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251230Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135770
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461624Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727116
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 23, 2017 | - - |
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 410080). This variant has not been reported in the literature in individuals affected with KIAA0196-related conditions. This variant is present in population databases (rs142883794, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 991 of the KIAA0196 protein (p.Ile991Thr). - |
WASHC5-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 16, 2023 | The WASHC5 c.2972T>C variant is predicted to result in the amino acid substitution p.Ile991Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-126051184-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 23, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at