rs7641844

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006514.4(SCN10A):c.884-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,605,174 control chromosomes in the GnomAD database, including 74,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7964 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66828 hom. )

Consequence

SCN10A
NM_006514.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.17

Publications

11 publications found

Variant links:

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SCN10A Gene-Disease associations (from GenCC):

episodic pain syndrome, familial, 2
Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
sodium channelopathy-related small fiber neuropathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

SCN10A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006514.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 3-38760760-A-G is Benign according to our data. Variant chr3-38760760-A-G is described in ClinVar as Benign. ClinVar VariationId is 260000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN10A	NM_006514.4	MANE Select	c.884-13T>C	intron	N/A	NP_006505.4	Q9Y5Y9
SCN10A	NM_001293306.2		c.884-13T>C	intron	N/A	NP_001280235.2	Q9Y5Y9
SCN10A	NM_001293307.2		c.884-13T>C	intron	N/A	NP_001280236.2	Q9Y5Y9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.884-13T>C	intron	N/A	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1		c.884-13T>C	intron	N/A	ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1		c.914-16T>C	intron	N/A	ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47846

AN:

151970

Hom.:

7948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.304

GnomAD2 exomes

AF:

0.327

AC:

81671

AN:

249692

AF XY:

0.326

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.293

AC:

425567

AN:

1453086

Hom.:

66828

Cov.:

AF XY:

0.295

AC XY:

213118

AN XY:

723482

show subpopulations

African (AFR)

AF:

0.355

AC:

11810

AN:

33278

American (AMR)

AF:

0.296

AC:

13243

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

9590

AN:

26074

East Asian (EAS)

AF:

0.693

AC:

27476

AN:

39632

South Asian (SAS)

AF:

0.359

AC:

30860

AN:

86064

European-Finnish (FIN)

AF:

0.270

AC:

14410

AN:

53272

Middle Eastern (MID)

AF:

0.287

AC:

1650

AN:

5748

European-Non Finnish (NFE)

AF:

0.270

AC:

298013

AN:

1104244

Other (OTH)

AF:

0.308

AC:

18515

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

13038

26076

39114

52152

65190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10224

20448

30672

40896

51120

<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:

0.315

AC:

47915

AN:

152088

Hom.:

7964

Cov.:

AF XY:

0.318

AC XY:

23667

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.338

AC:

13998

AN:

41474

American (AMR)

AF:

0.298

AC:

4551

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1295

AN:

3470

East Asian (EAS)

AF:

0.688

AC:

3554

AN:

5168

South Asian (SAS)

AF:

0.370

AC:

1781

AN:

4808

European-Finnish (FIN)

AF:

0.268

AC:

2831

AN:

10582

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18847

AN:

67976

Other (OTH)

AF:

0.303

AC:

641

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1645

3291

4936

6582

8227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.291

Hom.:

22991

Bravo

AF:

0.319

Asia WGS

AF:

0.492

AC:

1712

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Brugada syndrome (1)

Episodic pain syndrome, familial, 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.2

Mutation Taster

=74/26

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over