rs201531206

Variant names:

• chr2-166286540-G-A
• rs201531206
• NM_001365536.1:c.1398C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166286540-G-A
• chr2-166286540-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001365536.1(SCN9A):​c.1398C>T​(p.Ser466Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,610,208 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S466S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0025 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (19 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.405
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 2-166286540-G-A is Benign according to our data. Variant chr2-166286540-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.405 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AD,SD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.1398C>T	p.Ser466Ser	synonymous	Exon 11 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.1398C>T	p.Ser466Ser	synonymous	Exon 11 of 27	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1030-8025G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1398C>T	p.Ser466Ser	synonymous	Exon 11 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.1398C>T	p.Ser466Ser	synonymous	Exon 11 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.1398C>T	p.Ser466Ser	synonymous	Exon 11 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 151944 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00298 AC: 724 AN: 242982 AF XY: 0.00286

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.000849

GnomAD4 exome AF: 0.00153 AC: 2238 AN: 1458146 Hom.: 19 Cov.: 31 AF XY: 0.00150 AC XY: 1088 AN XY: 725294

African (AFR) AF: 0.000121 AC: 4 AN: 33094

American (AMR) AF: 0.0000909 AC: 4 AN: 44008

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26032

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85402

European-Finnish (FIN) AF: 0.0206 AC: 1095 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000961 AC: 1067 AN: 1110770

Other (OTH) AF: 0.00108 AC: 65 AN: 60180

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152062 Hom.: 4 Cov.: 32 AF XY: 0.00338 AC XY: 251 AN XY: 74358

African (AFR) AF: 0.000145 AC: 6 AN: 41466

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.0231 AC: 245 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00157 AC: 107 AN: 67970

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.000642

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)
-	-	1	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (1)
-	-	1	Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Paroxysmal extreme pain disorder (1)
-	-	1	Primary erythromelalgia (1)
-	-	1	Small fiber neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	6.4
DANN	Benign	0.84
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs201531206; hg19: chr2-167143050;