chr9-125189577-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002721.5(PPP6C):c.75+67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,606,740 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 (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
PPP6C
NM_002721.5 intron
NM_002721.5 intron
Scores
15
Clinical Significance
Conservation
PhyloP100: -0.0840
Genes affected
PPP6C (HGNC:9323): (protein phosphatase 6 catalytic subunit) This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.018592179).
BS2
?
High AC in GnomAd at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP6C | NM_002721.5 | c.75+67C>T | intron_variant | ENST00000373547.9 | |||
PPP6C | NM_001123355.2 | c.142C>T | p.Pro48Ser | missense_variant | 1/8 | ||
PPP6C | XM_047423566.1 | c.142C>T | p.Pro48Ser | missense_variant | 1/7 | ||
PPP6C | NM_001123369.2 | c.75+67C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP6C | ENST00000373547.9 | c.75+67C>T | intron_variant | 1 | NM_002721.5 | P1 | |||
PPP6C | ENST00000451402.5 | c.142C>T | p.Pro48Ser | missense_variant | 1/8 | 2 | |||
PPP6C | ENST00000415905.5 | c.75+67C>T | intron_variant | 2 | |||||
PPP6C | ENST00000456642.1 | c.-55+67C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152188Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000218 AC: 5AN: 229754Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126864
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1454434Hom.: 0 Cov.: 31 AF XY: 0.00000829 AC XY: 6AN XY: 723490
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74480
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2022 | The c.142C>T (p.P48S) alteration is located in exon 1 (coding exon 1) of the PPP6C gene. This alteration results from a C to T substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at