rs766212849
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001365536.1(SCN9A):c.2454_2458delAAGTT(p.Leu818PhefsTer38) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,268 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
SCN9A
NM_001365536.1 frameshift
NM_001365536.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.02
Publications
1 publications found
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 was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-166278198-AAACTT-A is Pathogenic according to our data. Variant chr2-166278198-AAACTT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 471099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN9A | MANE Select | c.2454_2458delAAGTT | p.Leu818PhefsTer38 | frameshift | Exon 15 of 27 | NP_001352465.1 | Q15858-1 | ||
| SCN9A | c.2421_2425delAAGTT | p.Leu807PhefsTer38 | frameshift | Exon 15 of 27 | NP_002968.2 | Q15858-3 | |||
| SCN1A-AS1 | n.1029+954_1029+958delCTTAA | intron | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN9A | MANE Select | c.2454_2458delAAGTT | p.Leu818PhefsTer38 | frameshift | Exon 15 of 27 | ENSP00000495601.1 | Q15858-1 | ||
| SCN9A | TSL:5 | c.2454_2458delAAGTT | p.Leu818PhefsTer38 | frameshift | Exon 15 of 27 | ENSP00000304748.7 | Q15858-1 | ||
| SCN9A | TSL:5 | c.2421_2425delAAGTT | p.Leu807PhefsTer38 | frameshift | Exon 15 of 27 | ENSP00000386306.1 | Q15858-3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152150
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74456 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152268
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74456
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41562
American (AMR)
AF:
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Channelopathy-associated congenital insensitivity to pain, autosomal recessive (1)
1
-
-
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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