chr9-92032567-A-G
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006415.4(SPTLC1):c.1329-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,034 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
SPTLC1
NM_006415.4 splice_polypyrimidine_tract, intron
NM_006415.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0002512
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 9-92032567-A-G is Benign according to our data. Variant chr9-92032567-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 380134.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000657 (10/152174) while in subpopulation AMR AF= 0.000131 (2/15280). AF 95% confidence interval is 0.0000476. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTLC1 | NM_006415.4 | c.1329-9T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000262554.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC1 | ENST00000262554.7 | c.1329-9T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006415.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251464Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135912
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GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727232
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74342
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Neuropathy, hereditary sensory and autonomic, type 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 01, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary sensory and autonomic neuropathy type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at