rs779810169
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The ENST00000262554.7(SPTLC1):c.472A>T(p.Thr158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T158A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000262554.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTLC1 | NM_006415.4 | c.472A>T | p.Thr158Ser | missense_variant | 6/15 | ENST00000262554.7 | NP_006406.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.472A>T | p.Thr158Ser | missense_variant | 6/15 | 1 | NM_006415.4 | ENSP00000262554 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251146Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135760
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461756Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727180
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neuropathy, hereditary sensory and autonomic, type 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Hereditary sensory and autonomic neuropathy type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 10, 2023 | ClinVar contains an entry for this variant (Variation ID: 576860). This variant has not been reported in the literature in individuals affected with SPTLC1-related conditions. This variant is present in population databases (rs779810169, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 158 of the SPTLC1 protein (p.Thr158Ser). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPTLC1 protein function. 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