rs12994338

Variant names:

• chr2-166303519-T-C
• rs12994338
• NM_001365536.1:c.689-217A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-166303519-T-C
• chr2-166303519-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365536.1(SCN9A):​c.689-217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,062 control chromosomes in the GnomAD database, including 46,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46024 hom., cov: 31)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.689-217A>G		intron_variant	Intron 6 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.689-217A>G		intron_variant	Intron 6 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.689-217A>G		intron_variant	Intron 6 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.689-217A>G		intron_variant	Intron 6 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.689-217A>G		intron_variant	Intron 6 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.689-217A>G		intron_variant	Intron 6 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.689-217A>G		intron_variant	Intron 7 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117828 AN: 151944 Hom.: 45989 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.773

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.775 AC: 117918 AN: 152062 Hom.: 46024 Cov.: 31 AF XY: 0.776 AC XY: 57685 AN XY: 74314

African (AFR) AF: 0.877 AC: 36440 AN: 41528

American (AMR) AF: 0.734 AC: 11192 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2813 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3971 AN: 5176

South Asian (SAS) AF: 0.797 AC: 3838 AN: 4818

European-Finnish (FIN) AF: 0.745 AC: 7854 AN: 10542

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 49420 AN: 67966

Other (OTH) AF: 0.776 AC: 1637 AN: 2110

Alfa AF: 0.744 Hom.: 102971

Bravo AF: 0.778

Asia WGS AF: 0.789 AC: 2739 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs12994338; hg19: chr2-167160029;