NM_001365536.1:c.4399-335T>C

Variant names:

• chr2-166204799-A-G
• rs16851778
• NM_001365536.1:c.4399-335T>C

Variant summary

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

The NM_001365536.1(SCN9A):​c.4399-335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 157,104 control chromosomes in the GnomAD database, including 2,478 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 0.16 (2377 hom., cov: 32)
  • Exomes 𝑓: 0.19 (101 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 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.4399-335T>C		intron	N/A	NP_001352465.1
	SCN9A	NM_002977.4		c.4366-335T>C		intron	N/A	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.611+4981A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.4399-335T>C		intron	N/A	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.4399-335T>C		intron	N/A	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.4366-335T>C		intron	N/A	ENSP00000386306.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24171 AN: 151970 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.191 AC: 960 AN: 5016 Hom.: 101 Cov.: 0 AF XY: 0.194 AC XY: 522 AN XY: 2686

African (AFR) AF: 0.0573 AC: 11 AN: 192

American (AMR) AF: 0.149 AC: 26 AN: 174

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 22 AN: 184

East Asian (EAS) AF: 0.431 AC: 113 AN: 262

South Asian (SAS) AF: 0.198 AC: 17 AN: 86

European-Finnish (FIN) AF: 0.246 AC: 28 AN: 114

Middle Eastern (MID) AF: 0.222 AC: 4 AN: 18

European-Non Finnish (NFE) AF: 0.186 AC: 678 AN: 3654

Other (OTH) AF: 0.184 AC: 61 AN: 332

GnomAD4 genome AF: 0.159 AC: 24181 AN: 152088 Hom.: 2377 Cov.: 32 AF XY: 0.165 AC XY: 12278 AN XY: 74338

African (AFR) AF: 0.0548 AC: 2274 AN: 41526

American (AMR) AF: 0.156 AC: 2380 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1755 AN: 5164

South Asian (SAS) AF: 0.198 AC: 954 AN: 4826

European-Finnish (FIN) AF: 0.272 AC: 2874 AN: 10566

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12819 AN: 67952

Other (OTH) AF: 0.152 AC: 320 AN: 2106

Alfa AF: 0.175 Hom.: 6946

Bravo AF: 0.148

Asia WGS AF: 0.240 AC: 831 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		-0.90
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: rs16851778; hg19: chr2-167061309;