rs587777848
Variant summary
Our verdict is Pathogenic. Variant got 27 ACMG points: 27P and 0B. PS1_Very_StrongPM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_004975.4(KCNB1):c.1041C>A(p.Ser347Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S347I) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004975.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 27 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.1041C>A | p.Ser347Arg | missense_variant | 2/2 | ENST00000371741.6 | |
LOC105372649 | XR_001754659.2 | n.1201+42495G>T | intron_variant, non_coding_transcript_variant | ||||
KCNB1 | XM_011528799.3 | c.1041C>A | p.Ser347Arg | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.1041C>A | p.Ser347Arg | missense_variant | 2/2 | 1 | NM_004975.4 | P1 | |
KCNB1 | ENST00000635465.1 | c.1041C>A | p.Ser347Arg | missense_variant | 3/3 | 1 | P1 | ||
ENST00000637341.1 | n.206+42495G>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
KCNB1 | ENST00000635878.1 | c.97-75136C>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 26 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Scripps Translational Science Institute, Scripps Health and The Scripps Research Institute | Dec 15, 2015 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2014 | - - |
Neurodevelopmental delay Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | - | - - |
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2018 | - - |
not provided Other:1
not provided, no classification provided | in vitro | Kearney Laboratory, Northwestern University Feinberg School of Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at