22-21939563-GTCC-GTCCTCC
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_014634.4(PPM1F):c.321_323dupGGA(p.Glu107dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,581,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000098 ( 0 hom. )
Consequence
PPM1F
NM_014634.4 disruptive_inframe_insertion
NM_014634.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.88
Genes affected
PPM1F (HGNC:19388): (protein phosphatase, Mg2+/Mn2+ dependent 1F) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_014634.4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPM1F | NM_014634.4 | c.321_323dupGGA | p.Glu107dup | disruptive_inframe_insertion | Exon 3 of 8 | ENST00000263212.10 | NP_055449.1 | |
PPM1F | NM_001410836.1 | c.-184_-182dupGGA | 5_prime_UTR_variant | Exon 2 of 7 | NP_001397765.1 | |||
PPM1F-AS1 | NR_147620.1 | n.1336_1338dupCTC | non_coding_transcript_exon_variant | Exon 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000356 AC: 7AN: 196490Hom.: 0 AF XY: 0.0000286 AC XY: 3AN XY: 104786
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GnomAD4 exome AF: 0.00000979 AC: 14AN: 1429656Hom.: 0 Cov.: 31 AF XY: 0.00000847 AC XY: 6AN XY: 707968
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74324
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at