Variant 19-35030823-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001037.5(SCN1B):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCN1B
NM_001037.5 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

SCN1B (HGNC:10586): (sodium voltage-gated channel beta subunit 1) Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

SCN1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-35030823-G-A is Pathogenic according to our data. Variant chr19-35030823-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2891167.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/6	ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/3		NP_950238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/6	1	NM_001037.5	ENSP00000262631	P1	Q07699-1
SCN1B	ENST00000415950.5 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/3	1		ENSP00000396915		Q07699-2
SCN1B	ENST00000638536.1 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/5	1		ENSP00000492022	P1	Q07699-1
SCN1B	ENST00000595652.5 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/6	2		ENSP00000468848

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

936554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

457422

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome 5

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2023

For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individuals with clinical features of generalized epilepsy with febrile seizures plus (PMID: 30660056; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SCN1B mRNA. The next in-frame methionine is located at codon 34. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.60

BayesDel_noAF

Pathogenic

0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Pathogenic

1.0

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Uncertain

0.50

MutationTaster

Benign

1.0

D;D

PROVEAN

Benign

-1.3

N;.;N;.

REVEL

Uncertain

0.59

Sift

Benign

0.049

D;.;D;.

Sift4G

Pathogenic

0.0

D;.;D;D

Polyphen

0.0070

B;B;B;B

Vest4

0.38

MutPred

0.90

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.93

ClinPred

0.88

GERP RS

2.3

Varity_R

0.42

gMVP

0.86

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over