rs1554711394
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006415.4(SPTLC1):c.386del(p.Gly129AlafsTer28) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G129G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006415.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.386del | p.Gly129AlafsTer28 | frameshift_variant | 5/15 | ENST00000262554.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.386del | p.Gly129AlafsTer28 | frameshift_variant | 5/15 | 1 | NM_006415.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461720Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727178
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 | May 21, 2019 | 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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SPTLC1 cause disease. A missense substitution downstream of this frameshift (p.Val144Asp) has been determined to be pathogenic (PMID: 11242114, 19132419, 25584079, 24673574, 26681808). This suggests that the Val144 residue is critical for SPTLC1 protein function and that other variants that cause disruption of this position may also be pathogenic. This variant has not been reported in the literature in individuals with SPTLC1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly129Alafs*28) in the SPTLC1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at