Variant rs201243874 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001365536.1(SCN9A):c.205G>T(p.Gly69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SCN9A
NM_001365536.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Variant links:

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]

SCN9A links:

SCN9A (HGNC:):

SCN9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCN9A	ENST00000642356.2 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/27		NM_001365536.1	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/27	5		ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/27	5		ENSP00000386306.1	Q15858-3
SCN9A	ENST00000645907.1 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/27			ENSP00000495983.1	Q15858-4
SCN9A	ENST00000454569.6 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	2/15	1		ENSP00000413212.2	A0A0C4DG82
SCN9A	ENST00000452182.2 linkuse as main transcript	c.205G>T	p.Gly69Cys	missense_variant	3/11	1		ENSP00000393141.2	H7C064

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461092

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

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

AF:

0.00000661

AC:

AN:

151356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73850

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

.;D;.;.;D;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.055

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.91

D;.;D;D;D;D;D;D

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Pathogenic

3.1

M;M;M;.;M;M;.;.

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.6

D;D;.;.;.;D;.;.

REVEL

Uncertain

0.52

Sift

Uncertain

0.0080

D;D;.;.;.;D;.;.

Sift4G

Uncertain

0.010

D;D;.;.;.;D;.;.

Vest4

0.44

MutPred

0.62

Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);Loss of disorder (P = 0.0468);

MVP

0.81

MPC

0.57

ClinPred

0.99

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over