rs200885240

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001365536.1(SCN9A):​c.253A>G​(p.Lys85Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SCN9A
NM_001365536.1 missense

Scores

2
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Publications

1 publications found
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]
SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SCN9A
NM_001365536.1
MANE Select
c.253A>Gp.Lys85Glu
missense
Exon 2 of 27NP_001352465.1Q15858-1
SCN9A
NM_002977.4
c.253A>Gp.Lys85Glu
missense
Exon 2 of 27NP_002968.2Q15858-3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SCN9A
ENST00000642356.2
MANE Select
c.253A>Gp.Lys85Glu
missense
Exon 2 of 27ENSP00000495601.1Q15858-1
SCN9A
ENST00000303354.11
TSL:5
c.253A>Gp.Lys85Glu
missense
Exon 2 of 27ENSP00000304748.7Q15858-1
SCN9A
ENST00000409672.5
TSL:5
c.253A>Gp.Lys85Glu
missense
Exon 2 of 27ENSP00000386306.1Q15858-3

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
7.11e-7
AC:
1
AN:
1406296
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
695180
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32112
American (AMR)
AF:
0.00
AC:
0
AN:
41042
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24242
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
74566
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4868
European-Non Finnish (NFE)
AF:
9.25e-7
AC:
1
AN:
1080984
Other (OTH)
AF:
0.00
AC:
0
AN:
57628
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
24
Alfa
AF:
0.0000355
Hom.:
0

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T
Eigen
Benign
0.096
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.88
D
M_CAP
Uncertain
0.21
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Pathogenic
0.88
D
MutationAssessor
Uncertain
2.6
M
PhyloP100
1.7
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.52
Sift
Benign
0.035
D
Sift4G
Benign
0.23
T
Vest4
0.53
MVP
0.78
MPC
0.19
ClinPred
0.91
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.34
Mutation Taster
=50/50

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

Other links and lift over

dbSNP: rs200885240; hg19: chr2-167168014; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.