19-35033607-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5

The NM_001037.5(SCN1B):​c.316A>T​(p.Ile106Phe) variant causes a missense change. 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 (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SCN1B
NM_001037.5 missense

Scores

7
10
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1
In a disulfide_bond (size 81) in uniprot entity SCN1B_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_001037.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857
PP5
Variant 19-35033607-A-T is Pathogenic according to our data. Variant chr19-35033607-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 375687.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCN1BNM_001037.5 linkuse as main transcriptc.316A>T p.Ile106Phe missense_variant 3/6 ENST00000262631.11 NP_001028.1 Q07699-1
SCN1BNM_199037.5 linkuse as main transcriptc.316A>T p.Ile106Phe missense_variant 3/3 NP_950238.1 Q07699-2
SCN1BNM_001321605.2 linkuse as main transcriptc.217A>T p.Ile73Phe missense_variant 3/6 NP_001308534.1 Q07699A0A1W2PR05

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCN1BENST00000262631.11 linkuse as main transcriptc.316A>T p.Ile106Phe missense_variant 3/61 NM_001037.5 ENSP00000262631.3 Q07699-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 52 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 09, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.44
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T;T;.;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
.;D;D;D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.86
D;D;D;D;D
MetaSVM
Pathogenic
0.85
D
MutationAssessor
Benign
2.0
M;M;M;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.4
D;.;D;.;.
REVEL
Pathogenic
0.88
Sift
Uncertain
0.0030
D;.;D;.;.
Sift4G
Uncertain
0.019
D;.;D;.;.
Polyphen
1.0
D;D;D;.;.
Vest4
0.83
MutPred
0.62
Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);.;.;
MVP
0.98
MPC
2.0
ClinPred
0.95
D
GERP RS
4.5
Varity_R
0.67
gMVP
0.99

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.

Other links and lift over

dbSNP: rs931949929; hg19: chr19-35524511; API