8-22539481-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005605.5(PPP3CC):c.1334C>T(p.Ala445Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
PPP3CC
NM_005605.5 missense
NM_005605.5 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 5.08
Genes affected
PPP3CC (HGNC:9316): (protein phosphatase 3 catalytic subunit gamma) Calcineurin is a calcium-dependent, calmodulin-stimulated protein phosphatase involved in the downstream regulation of dopaminergic signal transduction. Calcineurin is composed of a regulatory subunit and a catalytic subunit. The protein encoded by this gene represents one of the regulatory subunits that has been found for calcineurin. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP3CC | NM_005605.5 | c.1334C>T | p.Ala445Val | missense_variant | 13/14 | ENST00000240139.10 | |
LOC124901905 | XR_007060851.1 | n.1964+12681G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP3CC | ENST00000240139.10 | c.1334C>T | p.Ala445Val | missense_variant | 13/14 | 1 | NM_005605.5 | P3 | |
ENST00000664810.1 | n.93+13871G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251256Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135806
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727154
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74434
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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 | Nov 03, 2023 | The c.1334C>T (p.A445V) alteration is located in exon 13 (coding exon 13) of the PPP3CC gene. This alteration results from a C to T substitution at nucleotide position 1334, causing the alanine (A) at amino acid position 445 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Uncertain
D;T
Polyphen
D;.
Vest4
MVP
MPC
0.32
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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