chr13-23375207-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_014363.6(SACS):c.83C>T(p.Ser28Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,501,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. S28S) has been classified as Likely benign.
Frequency
Consequence
NM_014363.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SACS | NM_014363.6 | c.83C>T | p.Ser28Phe | missense_variant | 3/10 | ENST00000382292.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SACS | ENST00000382292.9 | c.83C>T | p.Ser28Phe | missense_variant | 3/10 | 5 | NM_014363.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151990Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000795 AC: 8AN: 100604Hom.: 0 AF XY: 0.0000536 AC XY: 3AN XY: 55934
GnomAD4 exome AF: 0.0000296 AC: 40AN: 1349316Hom.: 0 Cov.: 31 AF XY: 0.0000255 AC XY: 17AN XY: 665376
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151990Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74242
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.83C>T (p.S28F) alteration is located in exon 3 (coding exon 2) of the SACS gene. This alteration results from a C to T substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Charlevoix-Saguenay spastic ataxia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at