rs1311057424

Variant names:

• chr12-110731829-C-G
• rs1311057424
• NM_002710.4:c.128G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-110731829-C-G
• chr12-110731829-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002710.4(PPP1CC):​c.128G>C​(p.Arg43Pro) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1CC NM_002710.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.87
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	NM_002710.4	MANE Select	c.128G>C	p.Arg43Pro	missense	Exon 2 of 7	NP_002701.1	P36873-1
	PPP1CC	NM_001244974.2		c.128G>C	p.Arg43Pro	missense	Exon 2 of 8	NP_001231903.1	P36873-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CC	ENST00000335007.10	TSL:1 MANE Select	c.128G>C	p.Arg43Pro	missense	Exon 2 of 7	ENSP00000335084.5	P36873-1
	PPP1CC	ENST00000340766.9	TSL:2	c.128G>C	p.Arg43Pro	missense	Exon 2 of 8	ENSP00000341779.5	P36873-2
	PPP1CC	ENST00000546933.5	TSL:3	c.155G>C	p.Arg52Pro	missense	Exon 1 of 6	ENSP00000447122.1	F8W0W8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	4.8	H
PhyloP100		7.9
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.86
MutPred		0.65		Gain of catalytic residue at L40 (P = 0)
MVP		0.48
MPC		3.0
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.98
gMVP		0.97
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1311057424; hg19: chr12-111169634;