rs145316463
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001365536.1(SCN9A):c.2517+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,608,722 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001365536.1 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.2517+6C>T | splice_region_variant, intron_variant | Intron 15 of 26 | ENST00000642356.2 | NP_001352465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000454569.6 | c.2490C>T | p.Asn830Asn | synonymous_variant | Exon 15 of 15 | 1 | ENSP00000413212.2 | |||
SCN9A | ENST00000642356.2 | c.2517+6C>T | splice_region_variant, intron_variant | Intron 15 of 26 | NM_001365536.1 | ENSP00000495601.1 | ||||
SCN9A | ENST00000303354.11 | c.2517+6C>T | splice_region_variant, intron_variant | Intron 15 of 26 | 5 | ENSP00000304748.7 | ||||
SCN9A | ENST00000409672.5 | c.2484+6C>T | splice_region_variant, intron_variant | Intron 15 of 26 | 5 | ENSP00000386306.1 | ||||
SCN9A | ENST00000645907.1 | c.2484+6C>T | splice_region_variant, intron_variant | Intron 15 of 26 | ENSP00000495983.1 |
Frequencies
GnomAD3 genomes AF: 0.00431 AC: 655AN: 151978Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.000995 AC: 244AN: 245316Hom.: 0 AF XY: 0.000736 AC XY: 98AN XY: 133138
GnomAD4 exome AF: 0.000430 AC: 626AN: 1456626Hom.: 6 Cov.: 30 AF XY: 0.000380 AC XY: 275AN XY: 724548
GnomAD4 genome AF: 0.00434 AC: 660AN: 152096Hom.: 5 Cov.: 32 AF XY: 0.00424 AC XY: 315AN XY: 74336
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:1
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Primary erythromelalgia Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Channelopathy-associated congenital insensitivity to pain, autosomal recessive Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
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SCN9A-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Primary erythromelalgia;C1833661:Paroxysmal extreme pain disorder;C1855739:Channelopathy-associated congenital insensitivity to pain, autosomal recessive;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
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Small fiber neuropathy Benign:1
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Paroxysmal extreme pain disorder Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at