13-23333578-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014363.6(SACS):c.10298C>G(p.Thr3433Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014363.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250782Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135524
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461450Hom.: 0 Cov.: 57 AF XY: 0.0000179 AC XY: 13AN XY: 727038
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Charlevoix-Saguenay spastic ataxia Uncertain:2
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Spastic paraplegia Uncertain:1
This sequence change replaces threonine with arginine at codon 3433 of the SACS protein (p.Thr3433Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 411695). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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