rs776109731
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001365536.1(SCN9A):āc.1454A>Gā(p.Gln485Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,856 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000014 ( 1 hom. )
Consequence
SCN9A
NM_001365536.1 missense
NM_001365536.1 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 6.17
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 2-166286484-T-C is Benign according to our data. Variant chr2-166286484-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 471084.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.1454A>G | p.Gln485Arg | missense_variant | 11/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.1030-8081T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.1454A>G | p.Gln485Arg | missense_variant | 11/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1708-8081T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000482 AC: 12AN: 248860Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135026
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461564Hom.: 1 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727054
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;.;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;D;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;T;.
Sift4G
Benign
T;T;.;.;.;T;.
Polyphen
0.20
.;B;.;.;B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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