2-166284527-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365536.1(SCN9A):​c.1900C>G​(p.Arg634Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R634H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SCN9A
NM_001365536.1 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.92
Variant links:
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]
SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24511427).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCN9ANM_001365536.1 linkc.1900C>G p.Arg634Gly missense_variant 12/27 ENST00000642356.2 NP_001352465.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCN9AENST00000642356.2 linkc.1900C>G p.Arg634Gly missense_variant 12/27 NM_001365536.1 ENSP00000495601.1 Q15858-1
SCN9AENST00000303354.11 linkc.1900C>G p.Arg634Gly missense_variant 12/275 ENSP00000304748.7 Q15858-1
SCN9AENST00000409672.5 linkc.1900C>G p.Arg634Gly missense_variant 12/275 ENSP00000386306.1 Q15858-3
SCN9AENST00000645907.1 linkc.1900C>G p.Arg634Gly missense_variant 12/27 ENSP00000495983.1 Q15858-4
SCN9AENST00000454569.6 linkc.1900C>G p.Arg634Gly missense_variant 12/151 ENSP00000413212.2 A0A0C4DG82

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
.;T;.;.;T;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
0.041
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.45
T;.;T;T;T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
-0.34
N;N;N;.;N;N;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
1.5
N;.;.;.;.;N;.
REVEL
Uncertain
0.33
Sift
Benign
0.20
T;.;.;.;.;T;.
Sift4G
Benign
0.44
T;T;.;.;.;T;.
Polyphen
0.0
.;B;.;.;B;.;.
Vest4
0.32
MVP
0.73
MPC
0.15
ClinPred
0.67
D
GERP RS
5.7
Varity_R
0.18
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371543591; hg19: chr2-167141037; API