13-23336594-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014363.6(SACS):āc.7282A>Gā(p.Ile2428Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I2428I) has been classified as Likely benign.
Frequency
Consequence
NM_014363.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SACS | NM_014363.6 | c.7282A>G | p.Ile2428Val | missense_variant | 10/10 | ENST00000382292.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SACS | ENST00000382292.9 | c.7282A>G | p.Ile2428Val | missense_variant | 10/10 | 5 | NM_014363.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250166Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135420
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461414Hom.: 0 Cov.: 37 AF XY: 0.0000165 AC XY: 12AN XY: 726974
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 03, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 01, 2020 | - - |
Charlevoix-Saguenay spastic ataxia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 10, 2020 | - - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at