chr2-166284527-G-C

Variant names:

• chr2-166284527-G-C
• rs371543591
• NM_001365536.1:c.1900C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. R634C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• Publications: 2 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]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 27			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.1900C>G	p.Arg634Gly	missense_variant	Exon 12 of 15	1		ENSP00000413212.2

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	0.0	.;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;.
PhyloP100		3.9
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;.
Vest4		0.32
ClinPred		0.67	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.70
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs371543591; hg19: chr2-167141037;