2-166196349-C-A

Variant names:

• chr2-166196349-C-A
• rs142172527
• NM_001365536.1:c.*2323G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001365536.1(SCN9A):​c.*2323G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 151,786 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (14 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SCN9A NM_001365536.1 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:4
• Conservation: PhyloP100: -1.51
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-166196349-C-A is Benign according to our data. Variant chr2-166196349-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 331911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00717 (1089/151786) while in subpopulation SAS AF = 0.0525 (252/4802). AF 95% confidence interval is 0.0472. There are 14 homozygotes in GnomAd4. There are 567 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 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.*2323G>T		3_prime_UTR	Exon 27 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.*2323G>T		3_prime_UTR	Exon 27 of 27	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.432-3290C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.*2323G>T		3_prime_UTR	Exon 27 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.*2323G>T		3_prime_UTR	Exon 27 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.*2323G>T		3_prime_UTR	Exon 27 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.00716 AC: 1086 AN: 151666 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00605

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.000476

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00717 AC: 1089 AN: 151786 Hom.: 14 Cov.: 32 AF XY: 0.00764 AC XY: 567 AN XY: 74198

African (AFR) AF: 0.00493 AC: 204 AN: 41366

American (AMR) AF: 0.00604 AC: 92 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3466

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5174

South Asian (SAS) AF: 0.0525 AC: 252 AN: 4802

European-Finnish (FIN) AF: 0.000476 AC: 5 AN: 10510

Middle Eastern (MID) AF: 0.0176 AC: 5 AN: 284

European-Non Finnish (NFE) AF: 0.00420 AC: 285 AN: 67934

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00471 Hom.: 2

Bravo AF: 0.00633

Asia WGS AF: 0.0370 AC: 130 AN: 3464

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (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	-0.83
CADD	Benign	0.41
DANN	Benign	0.75
PhyloP100		-1.5
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: rs142172527; hg19: chr2-167052859;