19-35033607-A-T
Position:
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
NM_001037.5 missense
Scores
7
10
2
Clinical Significance
Conservation
PhyloP100: 4.61
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]
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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 |
---|---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.316A>T | p.Ile106Phe | missense_variant | 3/6 | ENST00000262631.11 | NP_001028.1 | |
SCN1B | NM_199037.5 | c.316A>T | p.Ile106Phe | missense_variant | 3/3 | NP_950238.1 | ||
SCN1B | NM_001321605.2 | c.217A>T | p.Ile73Phe | missense_variant | 3/6 | NP_001308534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.316A>T | p.Ile106Phe | missense_variant | 3/6 | 1 | NM_001037.5 | ENSP00000262631.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
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 provided | literature only | OMIM | Oct 09, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
M;M;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;D;.;.
Sift4G
Uncertain
D;.;D;.;.
Polyphen
D;D;D;.;.
Vest4
MutPred
Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);.;.;
MVP
MPC
2.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at