rs759028183
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_006415.4(SPTLC1):c.393G>T(p.Gly131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
SPTLC1
NM_006415.4 synonymous
NM_006415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.03
Genes affected
SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 9-92080050-C-A is Benign according to our data. Variant chr9-92080050-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 526706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.03 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000157 (23/1461758) while in subpopulation EAS AF= 0.000529 (21/39696). AF 95% confidence interval is 0.000354. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTLC1 | NM_006415.4 | c.393G>T | p.Gly131= | synonymous_variant | 5/15 | ENST00000262554.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.393G>T | p.Gly131= | synonymous_variant | 5/15 | 1 | NM_006415.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251360Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135850
GnomAD3 exomes
AF:
AC:
7
AN:
251360
Hom.:
AF XY:
AC XY:
2
AN XY:
135850
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461758Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727188
GnomAD4 exome
AF:
AC:
23
AN:
1461758
Hom.:
Cov.:
30
AF XY:
AC XY:
11
AN XY:
727188
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hereditary sensory and autonomic neuropathy type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at