rs201145311
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001365536.1(SCN9A):c.4356C>T(p.Phe1452=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000444 in 1,585,076 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 3 hom. )
Consequence
SCN9A
NM_001365536.1 synonymous
NM_001365536.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.87
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 Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 2-166226609-G-A is Benign according to our data. Variant chr2-166226609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 195815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00243 (370/152054) while in subpopulation AFR AF= 0.00851 (353/41498). AF 95% confidence interval is 0.00778. There are 3 homozygotes in gnomad4. There are 167 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.4356C>T | p.Phe1452= | synonymous_variant | 24/27 | ENST00000642356.2 | NP_001352465.1 | |
SCN1A-AS1 | NR_110260.1 | n.612-21586G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.4356C>T | p.Phe1452= | synonymous_variant | 24/27 | NM_001365536.1 | ENSP00000495601 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1290-21586G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00244 AC: 370AN: 151936Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000564 AC: 133AN: 235874Hom.: 3 AF XY: 0.000376 AC XY: 48AN XY: 127746
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GnomAD4 exome AF: 0.000233 AC: 334AN: 1433022Hom.: 3 Cov.: 27 AF XY: 0.000186 AC XY: 132AN XY: 711290
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GnomAD4 genome AF: 0.00243 AC: 370AN: 152054Hom.: 3 Cov.: 32 AF XY: 0.00225 AC XY: 167AN XY: 74328
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | SCN9A: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 01, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 02, 2015 | - - |
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at