NM_001365536.1:c.3157C>T
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001365536.1(SCN9A):c.3157C>T(p.Leu1053Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1053P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001365536.1 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.3157C>T | p.Leu1053Phe | missense_variant | Exon 17 of 27 | ENST00000642356.2 | NP_001352465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.3157C>T | p.Leu1053Phe | missense_variant | Exon 17 of 27 | NM_001365536.1 | ENSP00000495601.1 | |||
SCN9A | ENST00000303354.11 | c.3157C>T | p.Leu1053Phe | missense_variant | Exon 17 of 27 | 5 | ENSP00000304748.7 | |||
SCN9A | ENST00000409672.5 | c.3124C>T | p.Leu1042Phe | missense_variant | Exon 17 of 27 | 5 | ENSP00000386306.1 | |||
SCN9A | ENST00000645907.1 | c.3124C>T | p.Leu1042Phe | missense_variant | Exon 17 of 27 | ENSP00000495983.1 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151812Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000322 AC: 8AN: 248664 AF XY: 0.0000297 show subpopulations
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461396Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726966 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000790 AC: 12AN: 151812Hom.: 0 Cov.: 31 AF XY: 0.0000675 AC XY: 5AN XY: 74088 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.L1042F variant (also known as c.3124C>T), located in coding exon 16 of the SCN9A gene, results from a C to T substitution at nucleotide position 3124. The leucine at codon 1042 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at