rs6432901

chr2-166311583-C-Gchr2-166311583-C-T

Variant summary

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

The NM_001365536.1(SCN9A):c.174G>C(p.Gln58His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q58Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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=0.19155174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1	c.174G>C	p.Gln58His	missense_variant	2/27	ENST00000642356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2	c.174G>C	p.Gln58His	missense_variant	2/27		NM_001365536.1	P1
SCN1A-AS1	ENST00000651574.1	n.1977+15454C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461630 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 727100

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.86	D;.;D;D;D;D;D;D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.0	M;M;M;.;M;M;.;.
MutationTaster	Benign	0.91	P;P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N;N;.;.;.;N;.;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0060	D;D;.;.;.;D;.;.
Sift4G	Benign	0.070	T;T;.;.;.;T;.;.
Vest4		0.23
MutPred		0.33		Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);Gain of glycosylation at K57 (P = 0.1844);
MVP		0.69
MPC		0.17
ClinPred		0.32	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs6432901; hg19: chr2-167168093;