rs28702860

Positions:

• chr12-110722630-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002710.4(PPP1CC):​c.589G>A​(p.Asp197Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1CC NM_002710.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PPP1CC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1CC	NM_002710.4	c.589G>A	p.Asp197Asn	missense_variant	5/7	ENST00000335007.10	NP_002701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1CC	ENST00000335007.10	c.589G>A	p.Asp197Asn	missense_variant	5/7	1	NM_002710.4	ENSP00000335084.5
PPP1CC	ENST00000550261.5	n.*8G>A		non_coding_transcript_exon_variant	2/5	5		ENSP00000447528.2
PPP1CC	ENST00000550261.5	n.*8G>A		3_prime_UTR_variant	2/5	5		ENSP00000447528.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.85	D;.;T;D;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M;M;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.8	D;D;.;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;.;D;D;D
Sift4G	Benign	0.10	T;T;D;T;T;T
Polyphen		0.95	P;.;.;.;.;.
Vest4		0.66
MutPred		0.49		Gain of catalytic residue at V195 (P = 0.0067);Gain of catalytic residue at V195 (P = 0.0067);.;.;Gain of catalytic residue at V195 (P = 0.0067);Gain of catalytic residue at V195 (P = 0.0067);
MVP		0.61
MPC		1.8
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.90
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs28702860; hg19: chr12-111160435;