chr2-166228708-G-A

Variant names:

• chr2-166228708-G-A
• rs199800370
• NM_001365536.1:c.4189C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365536.1(SCN9A):​c.4189C>T​(p.Leu1397Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000342 in 1,459,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

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.4189C>T	p.Leu1397Leu	synonymous	Exon 22 of 27	NP_001352465.1
	SCN9A	NM_002977.4		c.4156C>T	p.Leu1386Leu	synonymous	Exon 22 of 27	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.612-19487G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.4189C>T	p.Leu1397Leu	synonymous	Exon 22 of 27	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.4189C>T	p.Leu1397Leu	synonymous	Exon 22 of 27	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.4156C>T	p.Leu1386Leu	synonymous	Exon 22 of 27	ENSP00000386306.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1459976 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726074

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110652

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.2
DANN	Benign	0.83
PhyloP100		6.9
Mutation Taster		=95/5	polymorphism

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: rs199800370; hg19: chr2-167085218;