NM_017607.4:c.2129A>C

Variant names:

• chr19-55092253-T-G
• rs1478737074
• NM_017607.4:c.2129A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017607.4(PPP1R12C):​c.2129A>C​(p.Gln710Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,588,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPP1R12C NM_017607.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

PPP1R12C (HGNC:14947): (protein phosphatase 1 regulatory subunit 12C) The gene encodes a subunit of myosin phosphatase. The encoded protein regulates the catalytic activity of protein phosphatase 1 delta and assembly of the actin cytoskeleton. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

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_017607.4. 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
	PPP1R12C	NM_017607.4	MANE Select	c.2129A>C	p.Gln710Pro	missense	Exon 19 of 22	NP_060077.1	Q9BZL4-1
	PPP1R12C	NM_001271618.2		c.2123A>C	p.Gln708Pro	missense	Exon 19 of 22	NP_001258547.1	Q9BZL4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12C	ENST00000263433.8	TSL:1 MANE Select	c.2129A>C	p.Gln710Pro	missense	Exon 19 of 22	ENSP00000263433.1	Q9BZL4-1
	PPP1R12C	ENST00000592993.1	TSL:1	c.1991A>C	p.Gln664Pro	missense	Exon 19 of 22	ENSP00000465957.1	K7EL81
	PPP1R12C	ENST00000854894.1		c.2126A>C	p.Gln709Pro	missense	Exon 19 of 22	ENSP00000524953.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436328 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 712806

African (AFR) AF: 0.00 AC: 0 AN: 32940

American (AMR) AF: 0.00 AC: 0 AN: 41556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 38218

South Asian (SAS) AF: 0.00 AC: 0 AN: 83108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100986

Other (OTH) AF: 0.00 AC: 0 AN: 59334

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.033	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.14		Loss of MoRF binding (P = 0.0426)
MVP		0.48
MPC		1.2
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.69
gMVP		0.72
Mutation Taster		=54/46	polymorphism

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: rs1478737074; hg19: chr19-55603621;