19-46347135-G-GC
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006247.4(PPP5C):c.46dup(p.Arg16ProfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,604,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PPP5C
NM_006247.4 frameshift
NM_006247.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.382
Genes affected
PPP5C (HGNC:9322): (protein phosphatase 5 catalytic subunit) This gene encodes a serine/threonine phosphatase which is a member of the protein phosphatase catalytic subunit family. Proteins in this family participate in pathways regulated by reversible phosphorylation at serine and threonine residues; many of these pathways are involved in the regulation of cell growth and differentiation. The product of this gene has been shown to participate in signaling pathways in response to hormones or cellular stress, and elevated levels of this protein may be associated with breast cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP5C | NM_006247.4 | c.46dup | p.Arg16ProfsTer7 | frameshift_variant | 1/13 | ENST00000012443.9 | |
PPP5C | NM_001204284.2 | c.46dup | p.Arg16ProfsTer7 | frameshift_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP5C | ENST00000012443.9 | c.46dup | p.Arg16ProfsTer7 | frameshift_variant | 1/13 | 1 | NM_006247.4 | P1 | |
PPP5C | ENST00000478046.5 | c.42dup | p.Arg15ProfsTer7 | frameshift_variant, NMD_transcript_variant | 1/14 | 1 | |||
PPP5C | ENST00000391919.1 | c.-273dup | 5_prime_UTR_variant | 1/12 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1452376Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 721714
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PPP5C-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 01, 2023 | The PPP5C c.46dupC variant is predicted to result in a frameshift and premature protein termination (p.Arg16Profs*7). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0069% of alleles in individuals of European (Non-Finnish) descent in gnomAD; however, this data may not be reliable (http://gnomad.broadinstitute.org/variant/19-46850392-G-GC). Loss-of-function has not been established as a disease mechanism for this gene, and therefore the clinical significance of this variant is currently uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at