19-55092637-C-T

Variant names:

• chr19-55092637-C-T
• rs187012282
• NM_017607.4:c.1937G>A

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.1937G>A​(p.Arg646His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R646L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP1R12C NM_017607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=0.08038142).

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.1937G>A	p.Arg646His	missense	Exon 17 of 22	NP_060077.1	Q9BZL4-1
	PPP1R12C	NM_001271618.2		c.1931G>A	p.Arg644His	missense	Exon 17 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.1937G>A	p.Arg646His	missense	Exon 17 of 22	ENSP00000263433.1	Q9BZL4-1
	PPP1R12C	ENST00000592993.1	TSL:1	c.1799G>A	p.Arg600His	missense	Exon 17 of 22	ENSP00000465957.1	K7EL81
	PPP1R12C	ENST00000854894.1		c.1934G>A	p.Arg645His	missense	Exon 17 of 22	ENSP00000524953.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 144030 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381498 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 680144

African (AFR) AF: 0.00 AC: 0 AN: 31666

American (AMR) AF: 0.00 AC: 0 AN: 32114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21586

East Asian (EAS) AF: 0.00 AC: 0 AN: 37720

South Asian (SAS) AF: 0.00 AC: 0 AN: 73222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075146

Other (OTH) AF: 0.00 AC: 0 AN: 57108

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.97	L
PhyloP100		-1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.098
Sift	Benign	0.20	T
Sift4G	Uncertain	0.042	D
Polyphen		0.0	B
Vest4		0.085
MutPred		0.096		Gain of glycosylation at S651 (P = 0.1117)
MVP		0.71
MPC		0.42
ClinPred		0.091	T
GERP RS		-5.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.072
gMVP		0.17
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs187012282; hg19: chr19-55604005;