19-55092500-C-G

Variant names:

• chr19-55092500-C-G
• rs771894836
• NM_017607.4:c.1997G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017607.4(PPP1R12C):​c.1997G>C​(p.Arg666Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R666Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PPP1R12C NM_017607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1534571).

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.1997G>C	p.Arg666Pro	missense	Exon 18 of 22	NP_060077.1	Q9BZL4-1
	PPP1R12C	NM_001271618.2		c.1991G>C	p.Arg664Pro	missense	Exon 18 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.1997G>C	p.Arg666Pro	missense	Exon 18 of 22	ENSP00000263433.1	Q9BZL4-1
	PPP1R12C	ENST00000592993.1	TSL:1	c.1859G>C	p.Arg620Pro	missense	Exon 18 of 22	ENSP00000465957.1	K7EL81
	PPP1R12C	ENST00000854894.1		c.1994G>C	p.Arg665Pro	missense	Exon 18 of 22	ENSP00000524953.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456642 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 724302

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 85646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110128

Other (OTH) AF: 0.00 AC: 0 AN: 60068

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.7
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.047
Sift	Uncertain	0.012	D
Sift4G	Benign	0.14	T
Polyphen		0.31	B
Vest4		0.099
MutPred		0.28		Loss of MoRF binding (P = 0.0076)
MVP		0.52
MPC		0.71
ClinPred		0.15	T
GERP RS		-2.2
Varity_R		0.44
gMVP		0.35
Mutation Taster		=81/19	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: rs771894836; hg19: chr19-55603868;