19-55091549-C-T

Variant names:

• chr19-55091549-C-T
• NM_017607.4:c.2272G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017607.4(PPP1R12C):​c.2272G>A​(p.Asp758Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP1R12C NM_017607.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1429668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12C	NM_017607.4	c.2272G>A	p.Asp758Asn	missense_variant	Exon 22 of 22	ENST00000263433.8	NP_060077.1
PPP1R12C	NM_001271618.2	c.2266G>A	p.Asp756Asn	missense_variant	Exon 22 of 22		NP_001258547.1
PPP1R12C	XM_005259013.5	c.2269G>A	p.Asp757Asn	missense_variant	Exon 22 of 22		XP_005259070.1
PPP1R12C	XM_011527045.3	c.2269G>A	p.Asp757Asn	missense_variant	Exon 22 of 22		XP_011525347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12C	ENST00000263433.8	c.2272G>A	p.Asp758Asn	missense_variant	Exon 22 of 22	1	NM_017607.4	ENSP00000263433.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2272G>A (p.D758N) alteration is located in exon 22 (coding exon 22) of the PPP1R12C gene. This alteration results from a G to A substitution at nucleotide position 2272, causing the aspartic acid (D) at amino acid position 758 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.067
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.43	B;.
Vest4		0.12
MutPred		0.073		Gain of MoRF binding (P = 0.0458);.;
MVP		0.28
MPC		1.1
ClinPred		0.79	D
GERP RS		0.50
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.23
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55602917;