rs749806397
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001365536.1(SCN9A):c.3400_3405dupTTGCCT(p.Pro1135_Gly1136insLeuPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,520 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 1 hom. )
Consequence
SCN9A
NM_001365536.1 conservative_inframe_insertion
NM_001365536.1 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.55
Genes affected
SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001365536.1.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.3400_3405dupTTGCCT | p.Pro1135_Gly1136insLeuPro | conservative_inframe_insertion | 18/27 | ENST00000642356.2 | NP_001352465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.3400_3405dupTTGCCT | p.Pro1135_Gly1136insLeuPro | conservative_inframe_insertion | 18/27 | NM_001365536.1 | ENSP00000495601.1 | |||
SCN9A | ENST00000303354.11 | c.3400_3405dupTTGCCT | p.Pro1135_Gly1136insLeuPro | conservative_inframe_insertion | 18/27 | 5 | ENSP00000304748.7 | |||
SCN9A | ENST00000409672.5 | c.3367_3372dupTTGCCT | p.Pro1124_Gly1125insLeuPro | conservative_inframe_insertion | 18/27 | 5 | ENSP00000386306.1 | |||
SCN9A | ENST00000645907.1 | c.3367_3372dupTTGCCT | p.Pro1124_Gly1125insLeuPro | conservative_inframe_insertion | 18/27 | ENSP00000495983.1 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248206Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134632
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GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460528Hom.: 1 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726528
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GnomAD4 genome AF: 0.0000790 AC: 12AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74230
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 07, 2024 | This variant, c.3367_3372dup, results in the insertion of 2 amino acid(s) of the SCN9A protein (p.Leu1123_Pro1124dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs749806397, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 471111). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at