19-55091894-C-T

Variant names:

• chr19-55091894-C-T
• rs773125943
• NM_017607.4:c.2176G>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.2176G>A​(p.Ala726Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A726S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PPP1R12C NM_017607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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=0.07585293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12C	NM_017607.4	c.2176G>A	p.Ala726Thr	missense_variant	Exon 20 of 22	ENST00000263433.8	NP_060077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12C	ENST00000263433.8	c.2176G>A	p.Ala726Thr	missense_variant	Exon 20 of 22	1	NM_017607.4	ENSP00000263433.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000200 AC: 5 AN: 250286 Hom.: 0 AF XY: 0.0000369 AC XY: 5 AN XY: 135650

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460982 Hom.: 0 Cov.: 36 AF XY: 0.0000206 AC XY: 15 AN XY: 726810

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000416

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.085
Sift	Benign	0.33	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.95	P;.
Vest4		0.081
MutPred		0.080		Gain of phosphorylation at A726 (P = 0.0081);.;
MVP		0.37
MPC		1.1
ClinPred		0.39	T
GERP RS		4.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.068
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs773125943; hg19: chr19-55603262;