NM_001165963.4:c.1651_1653delTCC
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_001165963.4(SCN1A):c.1651_1653delTCC(p.Ser551del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
SCN1A
NM_001165963.4 conservative_inframe_deletion
NM_001165963.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.64
Publications
0 publications found
Genes affected
SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 5 uncertain in NM_001165963.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001165963.4. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001165963.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN1A | MANE Select | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 13 of 29 | NP_001159435.1 | P35498-1 | ||
| SCN1A | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 12 of 28 | NP_001189364.1 | P35498-1 | |||
| SCN1A | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 11 of 27 | NP_001340877.1 | P35498-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCN1A | MANE Select | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 13 of 29 | ENSP00000501589.1 | P35498-1 | ||
| SCN1A | TSL:5 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 12 of 28 | ENSP00000303540.4 | P35498-1 | ||
| SCN1A | TSL:5 | c.1651_1653delTCC | p.Ser551del | conservative_inframe_deletion | Exon 10 of 26 | ENSP00000364554.3 | P35498-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152128
Hom.:
Cov.:
32
Gnomad AFR
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Gnomad AMR
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Gnomad OTH
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152128
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68030
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
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0
1
1
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2
0.00
0.20
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0.60
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0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Developmental and epileptic encephalopathy (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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