rs758111758
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The ENST00000338037.11(PLCB1):āc.3422A>Cā(p.Lys1141Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,605,430 control chromosomes in the GnomAD database, including 1 homozygotes. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. K1141K) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000338037.11 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.3422A>C | p.Lys1141Thr | missense_variant, splice_region_variant | 31/32 | ENST00000338037.11 | NP_056007.1 | |
PLCB1 | NM_182734.3 | c.3422A>C | p.Lys1141Thr | missense_variant, splice_region_variant | 31/33 | NP_877398.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.3422A>C | p.Lys1141Thr | missense_variant, splice_region_variant | 31/32 | 1 | NM_015192.4 | ENSP00000338185 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 244884Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132482
GnomAD4 exome AF: 0.00000688 AC: 10AN: 1453172Hom.: 1 Cov.: 29 AF XY: 0.0000111 AC XY: 8AN XY: 723000
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74388
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 31, 2017 | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is present in population databases (rs758111758, ExAC no frequency) but has not been reported in the literature in individuals with a PLCB1-related disease. This sequence change replaces lysine with threonine at codon 1141 of the PLCB1 protein (p.Lys1141Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at