NM_001365536.1:c.689-134G>A

Variant names:

• chr2-166303436-C-T
• rs13017637
• NM_001365536.1:c.689-134G>A

Variant summary

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

The NM_001365536.1(SCN9A):​c.689-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 660,158 control chromosomes in the GnomAD database, including 57,326 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 0.37 (11169 hom., cov: 32)
  • Exomes 𝑓: 0.42 (46157 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.689-134G>A		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.689-134G>A		intron	N/A	NP_002968.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.689-134G>A		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.689-134G>A		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.689-134G>A		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55871 AN: 151844 Hom.: 11173 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.416 AC: 211447 AN: 508196 Hom.: 46157 AF XY: 0.417 AC XY: 112432 AN XY: 269894

African (AFR) AF: 0.239 AC: 2925 AN: 12246

American (AMR) AF: 0.314 AC: 4724 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 7015 AN: 15570

East Asian (EAS) AF: 0.164 AC: 4898 AN: 29790

South Asian (SAS) AF: 0.395 AC: 17581 AN: 44488

European-Finnish (FIN) AF: 0.444 AC: 15833 AN: 35674

Middle Eastern (MID) AF: 0.354 AC: 742 AN: 2094

European-Non Finnish (NFE) AF: 0.449 AC: 146345 AN: 325706

Other (OTH) AF: 0.413 AC: 11384 AN: 27576

GnomAD4 genome AF: 0.368 AC: 55879 AN: 151962 Hom.: 11169 Cov.: 32 AF XY: 0.366 AC XY: 27142 AN XY: 74234

African (AFR) AF: 0.229 AC: 9507 AN: 41472

American (AMR) AF: 0.339 AC: 5176 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3470

East Asian (EAS) AF: 0.177 AC: 917 AN: 5174

South Asian (SAS) AF: 0.389 AC: 1873 AN: 4820

European-Finnish (FIN) AF: 0.451 AC: 4747 AN: 10528

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30772 AN: 67914

Other (OTH) AF: 0.363 AC: 766 AN: 2108

Alfa AF: 0.415 Hom.: 33042

Bravo AF: 0.347

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.65
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: rs13017637; hg19: chr2-167159946; COSMIC: COSV104409013;