11-64927829-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_006244.4(PPP2R5B):āc.424C>Gā(p.Pro142Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,680 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. P142P) has been classified as Likely benign.
Frequency
Consequence
NM_006244.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP2R5B | NM_006244.4 | c.424C>G | p.Pro142Ala | missense_variant | 4/14 | ENST00000164133.7 | |
PPP2R5B | XM_047427199.1 | c.424C>G | p.Pro142Ala | missense_variant | 3/13 | ||
PPP2R5B | XM_011545132.3 | c.337C>G | p.Pro113Ala | missense_variant | 5/15 | ||
PPP2R5B | XM_047427200.1 | c.337C>G | p.Pro113Ala | missense_variant | 5/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP2R5B | ENST00000164133.7 | c.424C>G | p.Pro142Ala | missense_variant | 4/14 | 1 | NM_006244.4 | P1 | |
PPP2R5B | ENST00000526559.5 | c.424C>G | p.Pro142Ala | missense_variant | 4/5 | 5 | |||
PPP2R5B | ENST00000532850.1 | c.166C>G | p.Pro56Ala | missense_variant | 4/5 | 3 | |||
PPP2R5B | ENST00000528530.1 | n.96C>G | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251472Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135906
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459680Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726300
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PPP2R5B protein function. This variant has not been reported in the literature in individuals affected with PPP2R5B-related conditions. This variant is present in population databases (rs750257738, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 142 of the PPP2R5B protein (p.Pro142Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at