chr2-166272712-G-C

Position:

• chr2-166272712-G-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.3038C>G​(p.Ala1013Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=0.18260565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3038C>G	p.Ala1013Gly	missense_variant	17/27	ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1	n.870-4376G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3038C>G	p.Ala1013Gly	missense_variant	17/27		NM_001365536.1	ENSP00000495601	P1
SCN1A-AS1	ENST00000651574.1	n.1548-4376G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.34	.;T;.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T;.;T;T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	.;M;.;.;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.0	N;.;.;.;.;N
REVEL	Benign	0.26
Sift	Benign	0.13	T;.;.;.;.;T
Sift4G	Benign	0.46	T;T;.;.;.;T
Vest4		0.21
MutPred		0.56		Gain of methylation at K1006 (P = 0.1017);.;Gain of methylation at K1006 (P = 0.1017);Gain of methylation at K1006 (P = 0.1017);.;.;
MVP		0.55
MPC		0.12
ClinPred		0.16	T
GERP RS		4.5
Varity_R		0.20
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs202153871; hg19: chr2-167129222;