rs587780456

Variant names:

• chr2-166228854-T-A
• NM_001365536.1:c.4043A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166228854-T-A
• chr2-166228854-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365536.1(SCN9A):​c.4043A>T​(p.Tyr1348Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.4043A>T	p.Tyr1348Phe	missense_variant	Exon 22 of 27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.4043A>T	p.Tyr1348Phe	missense_variant	Exon 22 of 27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.4043A>T	p.Tyr1348Phe	missense_variant	Exon 22 of 27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.4010A>T	p.Tyr1337Phe	missense_variant	Exon 22 of 27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.4010A>T	p.Tyr1337Phe	missense_variant	Exon 22 of 27			ENSP00000495983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.68	.;D;.;.;D;.
Eigen	Benign	-0.038
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;.;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.5	.;L;.;.;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N;.;.;.;.;N
REVEL	Uncertain	0.57
Sift	Benign	0.036	D;.;.;.;.;D
Sift4G	Benign	0.54	T;T;.;.;.;T
Vest4		0.30
MutPred		0.77		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);.;.;.;
MVP		0.75
MPC		0.12
ClinPred		0.72	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-167085364;