2-166303111-C-G

Variant names:

• chr2-166303111-C-G
• NM_001365536.1:c.880G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365536.1(SCN9A):​c.880G>C​(p.Glu294Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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

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=0.13421798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 27			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.880G>C	p.Glu294Gln	missense_variant	Exon 7 of 15	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.880G>C	p.Glu294Gln	missense_variant	Exon 8 of 11	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451492 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	10
DANN	Benign	0.46
DEOGEN2	Uncertain	0.43	.;T;.;.;T;.;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	T;.;T;T;T;T;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.3	L;L;L;.;L;L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.59	N;.;.;.;.;N;.;.
REVEL	Uncertain	0.29
Sift	Benign	0.56	T;.;.;.;.;T;.;.
Sift4G	Benign	0.56	T;T;.;.;.;T;.;.
Polyphen		0.0	.;B;.;.;B;.;.;.
Vest4		0.24
MVP		0.58
MPC		0.12
ClinPred		0.076	T
GERP RS		3.1
Varity_R		0.27
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-167159621;