Variant 3-38846736-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001349253.2(SCN11A):c.5334G>A(p.Leu1778=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr3-38846736-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SCN11A	NM_001349253.2 linkuse as main transcript	c.5334G>A	p.Leu1778=	synonymous_variant	30/30	ENST00000302328.9	NP_001336182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN11A	ENST00000302328.9 linkuse as main transcript	c.5334G>A	p.Leu1778=	synonymous_variant	30/30	5	NM_001349253.2	ENSP00000307599	A2	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

GnomAD3 exomes

AF:

0.0371

AC:

9326

AN:

251144

Hom.:

426

AF XY:

0.0339

AC XY:

4603

AN XY:

135740

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 SAS exome

AF:

0.0369

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

Gnomad4 AFR exome

AF:

0.0776

Gnomad4 AMR exome

AF:

0.0510

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.0378

Gnomad4 FIN exome

AF:

0.00923

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0239

GnomAD4 genome

AF:

0.0389

AC:

5927

AN:

152216

Hom.:

226

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0790

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.0420

Gnomad4 FIN

AF:

0.00923

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0186

Hom.:

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.0

DANN

Benign

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over