Variant rs373827019 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001349253.2(SCN11A):c.1499G>T(p.Arg500Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SCN11A
NM_001349253.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3382196).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN11A	NM_001349253.2 linkuse as main transcript	c.1499G>T	p.Arg500Leu	missense_variant	15/30	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.1499G>T	p.Arg500Leu	missense_variant	15/30	5	NM_001349253.2	ENSP00000307599	A2	Q9UI33-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250908

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135594

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 SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

2.0

M;M;M

MutationTaster

Benign

0.77

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

N;N;N

REVEL

Uncertain

0.46

Sift

Benign

0.041

D;D;T

Sift4G

Benign

0.12

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.50

MutPred

0.38

Loss of phosphorylation at S502 (P = 0.0578);Loss of phosphorylation at S502 (P = 0.0578);Loss of phosphorylation at S502 (P = 0.0578);

MVP

0.95

MPC

0.58

ClinPred

0.73

GERP RS

5.1

Varity_R

0.21

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over