12-79779349-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_002480.3(PPP1R12A):c.2956-749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,289,018 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: PPP1R12A NM_002480.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.87

Genes affected

PPP1R12A (HGNC:7618): (protein phosphatase 1 regulatory subunit 12A) Myosin phosphatase target subunit 1, which is also called the myosin-binding subunit of myosin phosphatase, is one of the subunits of myosin phosphatase. Myosin phosphatase regulates the interaction of actin and myosin downstream of the guanosine triphosphatase Rho. The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP. RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 12-79779349-C-T is Benign according to our data. Variant chr12-79779349-C-T is described in ClinVar as [Benign]. Clinvar id is 2643188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R12A	NM_002480.3	c.2956-749G>A		intron_variant		ENST00000450142.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R12A	ENST00000450142.7	c.2956-749G>A		intron_variant		1	NM_002480.3	P3

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00122 AC: 156 AN: 128018 Hom.: 0 AF XY: 0.00116 AC XY: 81 AN XY: 70106

Gnomad AFR exome AF: 0.000329

Gnomad AMR exome AF: 0.000616

Gnomad ASJ exome AF: 0.00173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000402

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00211

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00213 AC: 2421 AN: 1136762 Hom.: 3 Cov.: 30 AF XY: 0.00206 AC XY: 1149 AN XY: 557634

Gnomad4 AFR exome AF: 0.000205

Gnomad4 AMR exome AF: 0.000637

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000249

Gnomad4 FIN exome AF: 0.00142

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74452

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.00147

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

PPP1R12A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs568265420; hg19: chr12-80173129;