chr20-8132680-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_015192.4(PLCB1):āc.29C>Gā(p.Ala10Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,452 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10S) has been classified as Likely benign.
Frequency
Consequence
NM_015192.4 missense
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 | UniProt |
---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.29C>G | p.Ala10Gly | missense_variant | 1/32 | ENST00000338037.11 | |
PLCB1 | NM_182734.3 | c.29C>G | p.Ala10Gly | missense_variant | 1/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.29C>G | p.Ala10Gly | missense_variant | 1/32 | 1 | NM_015192.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247862Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134678
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460452Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726608
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 10 of the PLCB1 protein (p.Ala10Gly). ClinVar contains an entry for this variant (Variation ID: 1400576). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at