3-38846736-C-T

Variant names:

Variant summary

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

The NM_001349253.2(SCN11A):c.5334G>A(p.Leu1778Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,614,054 control chromosomes in the GnomAD database, including 1,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 226 hom., cov: 32)

Exomes 𝑓: 0.021 ( 858 hom. )

Consequence

SCN11A
NM_001349253.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.137

Publications

8 publications found

Variant links:

Genes affected

SCN11A (HGNC:10583): (sodium voltage-gated channel alpha subunit 11) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is highly expressed in nociceptive neurons of dorsal root ganglia and trigeminal ganglia. It mediates brain-derived neurotrophic factor-evoked membrane depolarization and is a major effector of peripheral inflammatory pain hypersensitivity. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy type VII and familial episodic pain syndrome-3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

SCN11A Gene-Disease associations (from GenCC):

autosomal dominant hereditary sensory and autonomic neuropathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
familial episodic pain syndrome with predominantly lower limb involvement
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
hereditary sensory and autonomic neuropathy type 7
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
sodium channelopathy-related small fiber neuropathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCN11A links:

Genome browser will be placed here

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 3-38846736-C-T is Benign according to our data. Variant chr3-38846736-C-T is described in ClinVar as [Benign]. Clinvar id is 474748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.137 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN11A	NM_001349253.2 link	c.5334G>A	p.Leu1778Leu	synonymous_variant	Exon 30 of 30	ENST00000302328.9	NP_001336182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN11A	ENST00000302328.9 link	c.5334G>A	p.Leu1778Leu	synonymous_variant	Exon 30 of 30	5	NM_001349253.2	ENSP00000307599.3		Q9UI33-1

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5916

AN:

152098

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0790

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0430

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0371

AC:

9326

AN:

251144

AF XY:

0.0339

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.0558

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.00781

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0205

AC:

30025

AN:

1461838

Hom.:

858

Cov.:

AF XY:

0.0205

AC XY:

14908

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0776

AC:

2598

AN:

33476

American (AMR)

AF:

0.0510

AC:

2280

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

268

AN:

26136

East Asian (EAS)

AF:

0.147

AC:

5839

AN:

39694

South Asian (SAS)

AF:

0.0378

AC:

3261

AN:

86256

European-Finnish (FIN)

AF:

0.00923

AC:

493

AN:

53420

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5764

European-Non Finnish (NFE)

AF:

0.0124

AC:

13738

AN:

1111974

Other (OTH)

AF:

0.0239

AC:

1443

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1628

3257

4885

6514

8142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0389

AC:

5927

AN:

152216

Hom.:

226

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0790

AC:

3281

AN:

41534

American (AMR)

AF:

0.0289

AC:

441

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3468

East Asian (EAS)

AF:

0.165

AC:

854

AN:

5168

South Asian (SAS)

AF:

0.0420

AC:

202

AN:

4814

European-Finnish (FIN)

AF:

0.00923

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

866

AN:

68012

Other (OTH)

AF:

0.0289

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

288

576

863

1151

1439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0210

Hom.:

104

Bravo

AF:

0.0442

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.0

(source)

DANN

Benign

0.47

PhyloP100

0.14

Mutation Taster

=96/4

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

Publications

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3-38846736-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over