chr2-166306609-A-C

Variant names:

• chr2-166306609-A-C
• rs1351935203
• NM_001365536.1:c.378-10T>G

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.378-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,464 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Scores: Splicing: ADA: 0.1082
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829
• 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=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.378-10T>G		intron_variant	Intron 3 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.378-10T>G		intron_variant	Intron 3 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.378-10T>G		intron_variant	Intron 3 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.378-10T>G		intron_variant	Intron 3 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.378-10T>G		intron_variant	Intron 3 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.378-10T>G		intron_variant	Intron 3 of 14	1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.378-10T>G		intron_variant	Intron 4 of 10	1		ENSP00000393141.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383464 Hom.: 0 Cov.: 26 AF XY: 0.00000292 AC XY: 2 AN XY: 685896

African (AFR) AF: 0.00 AC: 0 AN: 31878

American (AMR) AF: 0.00 AC: 0 AN: 37510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25236

East Asian (EAS) AF: 0.00 AC: 0 AN: 37820

South Asian (SAS) AF: 0.00 AC: 0 AN: 79842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1057196

Other (OTH) AF: 0.00 AC: 0 AN: 57700

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.88
PhyloP100		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.11
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: rs1351935203; hg19: chr2-167163119;