rs752060724
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_001165963.4(SCN1A):āc.3530C>Gā(p.Pro1177Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.3530C>G | p.Pro1177Arg | missense_variant | 20/29 | ENST00000674923.1 | |
LOC102724058 | NR_110598.1 | n.190G>C | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.3530C>G | p.Pro1177Arg | missense_variant | 20/29 | NM_001165963.4 | P4 | ||
SCN1A-AS1 | ENST00000651574.1 | n.207G>C | non_coding_transcript_exon_variant | 2/19 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460706Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726620
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center for Statistical Genetics, Columbia University | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | SCN1A: PP1:Strong, PM2, PP2 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2017 | The p.P1177R variant (also known as c.3530C>G), located in coding exon 17 of the SCN1A gene, results from a C to G substitution at nucleotide position 3530. The proline at codon 1177 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at