rs1299193372
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001365536.1(SCN9A):c.4704C>T(p.Ser1568Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,812 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
SCN9A
NM_001365536.1 synonymous
NM_001365536.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.476
Publications
0 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: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 2-166204025-G-A is Benign according to our data. Variant chr2-166204025-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 471134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.476 with no splicing effect.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN9A | NM_001365536.1 | MANE Select | c.4704C>T | p.Ser1568Ser | synonymous | Exon 26 of 27 | NP_001352465.1 | ||
| SCN9A | NM_002977.4 | c.4671C>T | p.Ser1557Ser | synonymous | Exon 26 of 27 | NP_002968.2 | |||
| SCN1A-AS1 | NR_110260.1 | n.611+4207G>A | intron | N/A |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN9A | ENST00000642356.2 | MANE Select | c.4704C>T | p.Ser1568Ser | synonymous | Exon 26 of 27 | ENSP00000495601.1 | ||
| SCN9A | ENST00000303354.11 | TSL:5 | c.4704C>T | p.Ser1568Ser | synonymous | Exon 26 of 27 | ENSP00000304748.7 | ||
| SCN9A | ENST00000409672.5 | TSL:5 | c.4671C>T | p.Ser1557Ser | synonymous | Exon 26 of 27 | ENSP00000386306.1 |
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 151812Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
151812
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome 0.0000132 AC: 2AN: 151812Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74144 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
151812
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74144
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41388
American (AMR)
AF:
AC:
0
AN:
15228
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3458
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10594
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67830
Other (OTH)
AF:
AC:
0
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
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0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
AF:
Hom.:
Bravo
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ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
-
-
1
Inborn genetic diseases (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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