rs28702860

Variant names:

• chr12-110722630-C-T
• rs28702860
• NM_002710.4:c.589G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002710.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	NM_002710.4	MANE Select	c.589G>A	p.Asp197Asn	missense	Exon 5 of 7	NP_002701.1
	PPP1CC	NM_001244974.2		c.589G>A	p.Asp197Asn	missense	Exon 5 of 8	NP_001231903.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	ENST00000335007.10	TSL:1 MANE Select	c.589G>A	p.Asp197Asn	missense	Exon 5 of 7	ENSP00000335084.5
	PPP1CC	ENST00000550261.5	TSL:5	n.*8G>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000447528.2
	PPP1CC	ENST00000550261.5	TSL:5	n.*8G>A		3_prime_UTR	Exon 2 of 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 v4.9

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
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.10	T
Polyphen		0.95	P
Vest4		0.66
MutPred		0.49		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
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs28702860; hg19: chr12-111160435;