rs1257961099

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002708.4(PPP1CA):​c.782G>T​(p.Arg261Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

PPP1CA
NM_002708.4 missense

Scores

14
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.89
Variant links:
Genes affected
PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. 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. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1CANM_002708.4 linkc.782G>T p.Arg261Leu missense_variant Exon 6 of 7 ENST00000376745.9 NP_002699.1 P62136-1
PPP1CANM_001008709.2 linkc.815G>T p.Arg272Leu missense_variant Exon 6 of 7 NP_001008709.1 P62136-2A0A140VJS9
PPP1CANM_206873.2 linkc.650G>T p.Arg217Leu missense_variant Exon 5 of 6 NP_996756.1 P62136-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1CAENST00000376745.9 linkc.782G>T p.Arg261Leu missense_variant Exon 6 of 7 1 NM_002708.4 ENSP00000365936.4 P62136-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
.;D;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Uncertain
0.29
D
MutationAssessor
Pathogenic
4.6
.;H;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-6.7
D;D;D;D
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.87
MVP
0.72
MPC
2.4
ClinPred
1.0
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.96
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67166293; API