rs766476735
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006415.4(SPTLC1):āc.908T>Cā(p.Ile303Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,424 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I303F) has been classified as Uncertain significance.
Frequency
Consequence
NM_006415.4 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 |
---|---|---|---|---|---|---|---|
SPTLC1 | NM_006415.4 | c.908T>C | p.Ile303Thr | missense_variant | 10/15 | ENST00000262554.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.908T>C | p.Ile303Thr | missense_variant | 10/15 | 1 | NM_006415.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250972Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135630
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460218Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726548
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2020 | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SPTLC1-related disease. This variant is present in population databases (rs766476735, ExAC 0.01%). This sequence change replaces isoleucine with threonine at codon 303 of the SPTLC1 protein (p.Ile303Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at