Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000296122.10(PPP1CB):c.-195G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 313,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
6552
American (AMR)
AF:
0.00
AC:
0
AN:
13662
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
8644
East Asian (EAS)
AF:
0.00
AC:
0
AN:
15314
South Asian (SAS)
AF:
0.00
AC:
0
AN:
44284
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
17772
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1450
European-Non Finnish (NFE)
AF:
0.00000531
AC:
1
AN:
188206
Other (OTH)
AF:
0.00
AC:
0
AN:
17372
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.