rs759753811
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 5P and 7B. PM1PM2PP2BP4_ModerateBP6BS2
The NM_001330260.2(SCN8A):c.4634C>T(p.Thr1545Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001330260.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.4634C>T | p.Thr1545Ile | missense_variant | 26/27 | ENST00000627620.5 | NP_001317189.1 | |
SCN8A | NM_014191.4 | c.4634C>T | p.Thr1545Ile | missense_variant | 26/27 | ENST00000354534.11 | NP_055006.1 | |
SCN8A | NM_001177984.3 | c.4511C>T | p.Thr1504Ile | missense_variant | 25/26 | NP_001171455.1 | ||
SCN8A | NM_001369788.1 | c.4511C>T | p.Thr1504Ile | missense_variant | 25/26 | NP_001356717.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.4634C>T | p.Thr1545Ile | missense_variant | 26/27 | 1 | NM_014191.4 | ENSP00000346534.4 | ||
SCN8A | ENST00000627620.5 | c.4634C>T | p.Thr1545Ile | missense_variant | 26/27 | 5 | NM_001330260.2 | ENSP00000487583.2 | ||
SCN8A | ENST00000599343.5 | c.4667C>T | p.Thr1556Ile | missense_variant | 25/26 | 5 | ENSP00000476447.3 | |||
SCN8A | ENST00000355133.7 | c.4511C>T | p.Thr1504Ile | missense_variant | 24/25 | 1 | ENSP00000347255.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249220Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135192
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727138
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 18, 2017 | The p.T1545I variant (also known as c.4634C>T), located in coding exon 25 of the SCN8A gene, results from a C to T substitution at nucleotide position 4634. The threonine at codon 1545 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Developmental and epileptic encephalopathy, 13;C4310728:Seizures, benign familial infantile, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 15, 2018 | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at