9-92059261-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_006415.4(SPTLC1):c.608G>A(p.Arg203His) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,702 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 (★). Synonymous variant affecting the same amino acid position (i.e. R203R) has been classified as Likely benign.
Frequency
Consequence
NM_006415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTLC1 | NM_006415.4 | c.608G>A | p.Arg203His | missense_variant | 7/15 | ENST00000262554.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.608G>A | p.Arg203His | missense_variant | 7/15 | 1 | NM_006415.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251224Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135784
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461702Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727142
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 17, 2023 | This variant has not been reported in the literature in individuals affected with SPTLC1-related conditions. This variant is present in population databases (rs778759719, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 203 of the SPTLC1 protein (p.Arg203His). ClinVar contains an entry for this variant (Variation ID: 568972). 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. 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 expected to disrupt SPTLC1 protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at