2-166272694-T-G

Variant names:

• chr2-166272694-T-G
• NM_001365536.1:c.3056A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365536.1(SCN9A):​c.3056A>C​(p.Lys1019Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,318 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: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19804847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.3056A>C	p.Lys1019Thr	missense_variant	Exon 17 of 27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.3056A>C	p.Lys1019Thr	missense_variant	Exon 17 of 27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.3056A>C	p.Lys1019Thr	missense_variant	Exon 17 of 27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.3023A>C	p.Lys1008Thr	missense_variant	Exon 17 of 27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.3023A>C	p.Lys1008Thr	missense_variant	Exon 17 of 27			ENSP00000495983.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446318 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717688

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	.;T;.;.;T;.
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.66	T;.;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.6	.;M;.;.;M;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.2	D;.;.;.;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;.;.;.;.;D
Sift4G	Benign	0.14	T;T;.;.;.;T
Vest4		0.19
MutPred		0.46		Loss of MoRF binding (P = 0.0295);.;Loss of MoRF binding (P = 0.0295);Loss of MoRF binding (P = 0.0295);.;.;
MVP		0.64
MPC		0.26
ClinPred		0.73	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-167129204;