Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_001365536.1(SCN9A):c.258G>A(p.Lys86Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000518 in 1,544,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SCN9A
NM_001365536.1 splice_region, synonymous

Scores

Splicing: ADA: 0.4402

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.500

Publications

0 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]

SCN9A links:

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

SCN1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=-0.5 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.258G>A	p.Lys86Lys	splice_region synonymous	Exon 2 of 27	NP_001352465.1
	SCN9A	NM_002977.4		c.258G>A	p.Lys86Lys	splice_region synonymous	Exon 2 of 27	NP_002968.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN9A	ENST00000642356.2	MANE Select	c.258G>A	p.Lys86Lys	splice_region synonymous	Exon 2 of 27	ENSP00000495601.1
SCN9A	ENST00000303354.11	TSL:5	c.258G>A	p.Lys86Lys	splice_region synonymous	Exon 2 of 27	ENSP00000304748.7
SCN9A	ENST00000409672.5	TSL:5	c.258G>A	p.Lys86Lys	splice_region synonymous	Exon 2 of 27	ENSP00000386306.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150590

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000864

AC:

AN:

231554

AF XY:

0.00000796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000431

AC:

AN:

1393468

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

687916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31790

American (AMR)

AF:

0.00

AC:

AN:

39918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23750

East Asian (EAS)

AF:

0.00

AC:

AN:

38930

South Asian (SAS)

AF:

0.00

AC:

AN:

72118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4700

European-Non Finnish (NFE)

AF:

0.00000559

AC:

AN:

1074002

Other (OTH)

AF:

0.00

AC:

AN:

57042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40928

American (AMR)

AF:

0.00

AC:

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67626

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

-0.50

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.44

dbscSNV1_RF

Benign

0.47

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs199940586

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over