rs201560403
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001365536.1(SCN9A):c.2733C>T(p.Asn911=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,974 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
SCN9A
NM_001365536.1 synonymous
NM_001365536.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0560
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 -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 2-166277124-G-A is Benign according to our data. Variant chr2-166277124-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 471101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.056 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.2733C>T | p.Asn911= | synonymous_variant | 16/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.906G>A | non_coding_transcript_exon_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.2733C>T | p.Asn911= | synonymous_variant | 16/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1584G>A | non_coding_transcript_exon_variant | 15/19 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152030Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251164Hom.: 1 AF XY: 0.0000368 AC XY: 5AN XY: 135722
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GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727218
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74362
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 | Invitae | Nov 18, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at