rs373226693
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_014363.6(SACS):c.6178G>C(p.Val2060Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2060A) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SACS | NM_014363.6 | c.6178G>C | p.Val2060Leu | missense_variant | 10/10 | ENST00000382292.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SACS | ENST00000382292.9 | c.6178G>C | p.Val2060Leu | missense_variant | 10/10 | 5 | NM_014363.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248638Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134960
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460588Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 726552
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2022 | The c.6178G>C (p.V2060L) alteration is located in exon 10 (coding exon 9) of the SACS gene. This alteration results from a G to C substitution at nucleotide position 6178, causing the valine (V) at amino acid position 2060 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 09, 2018 | - - |
Charlevoix-Saguenay spastic ataxia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 21, 2020 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at