dbSNP rs59468016: SCN10A:p.Gly979Gly (chr3-38726756-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006514.4(SCN10A):c.2937C>T(p.Gly979Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,611,748 control chromosomes in the GnomAD database, including 50,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3711 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46752 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.358

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-38726756-G-A is Benign according to our data. Variant chr3-38726756-G-A is described in ClinVar as Benign. ClinVar VariationId is 259994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.358 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 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	HGVSp	Effect	Exon Rank	Protein	UniProt
SCN10A	NM_006514.4	MANE Select	c.2937C>T	p.Gly979Gly	synonymous	Exon 17 of 28	NP_006505.4	Q9Y5Y9
SCN10A	NM_001293306.2		c.2937C>T	p.Gly979Gly	synonymous	Exon 16 of 27	NP_001280235.2	Q9Y5Y9
SCN10A	NM_001293307.2		c.2643C>T	p.Gly881Gly	synonymous	Exon 15 of 26	NP_001280236.2	Q9Y5Y9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.2937C>T	p.Gly979Gly	synonymous	Exon 17 of 28	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000643924.1		c.2937C>T	p.Gly979Gly	synonymous	Exon 16 of 27	ENSP00000495595.1	A0A2R8Y6J6
SCN10A	ENST00000655275.1		c.2964C>T	p.Gly988Gly	synonymous	Exon 17 of 28	ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29586

AN:

152034

Hom.:

3711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.233

AC:

58345

AN:

250858

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.247

AC:

360494

AN:

1459596

Hom.:

46752

Cov.:

AF XY:

0.248

AC XY:

179590

AN XY:

725556

show subpopulations

African (AFR)

AF:

0.0376

AC:

1258

AN:

33436

American (AMR)

AF:

0.113

AC:

5039

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8689

AN:

26120

East Asian (EAS)

AF:

0.425

AC:

16854

AN:

39614

South Asian (SAS)

AF:

0.235

AC:

20269

AN:

86212

European-Finnish (FIN)

AF:

0.270

AC:

14413

AN:

53396

Middle Eastern (MID)

AF:

0.220

AC:

1265

AN:

5760

European-Non Finnish (NFE)

AF:

0.251

AC:

278474

AN:

1110106

Other (OTH)

AF:

0.236

AC:

14233

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15003

30006

45010

60013

75016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9398

18796

28194

37592

46990

<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:

0.194

AC:

29578

AN:

152152

Hom.:

3711

Cov.:

AF XY:

0.197

AC XY:

14622

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0476

AC:

1979

AN:

41540

American (AMR)

AF:

0.138

AC:

2112

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1180

AN:

3462

East Asian (EAS)

AF:

0.403

AC:

2071

AN:

5138

South Asian (SAS)

AF:

0.242

AC:

1166

AN:

4814

European-Finnish (FIN)

AF:

0.270

AC:

2855

AN:

10588

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17451

AN:

67998

Other (OTH)

AF:

0.191

AC:

404

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1149

2297

3446

4594

5743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.220

Hom.:

3380

Bravo

AF:

0.178

Asia WGS

AF:

0.263

AC:

917

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.248

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Brugada syndrome (1)

Cardiovascular phenotype (1)

Episodic pain syndrome, familial, 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

(source)

DANN

Benign

0.50

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(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