rs764250569
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_015192.4(PLCB1):c.1537G>A(p.Asp513Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,611,372 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D513G) has been classified as Uncertain significance.
Frequency
Consequence
NM_015192.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.1537G>A | p.Asp513Asn | missense_variant | 15/32 | ENST00000338037.11 | |
PLCB1 | NM_182734.3 | c.1537G>A | p.Asp513Asn | missense_variant | 15/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.1537G>A | p.Asp513Asn | missense_variant | 15/32 | 1 | NM_015192.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248816Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134560
GnomAD4 exome AF: 0.0000384 AC: 56AN: 1459246Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 725910
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 27, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 22, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 578131). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (rs764250569, gnomAD 0.006%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 513 of the PLCB1 protein (p.Asp513Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at