rs10778691

Variant names:

• chr12-79826108-G-T
• rs10778691
• NM_002480.3:c.792+2212C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002480.3(PPP1R12A):​c.792+2212C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,602 control chromosomes in the GnomAD database, including 17,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (17082 hom., cov: 32)
• Consequence: PPP1R12A NM_002480.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 publications found

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]

PPP1R12A Gene-Disease associations (from GenCC):

• genitourinary and/or brain malformation syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002480.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12A	NM_002480.3	MANE Select	c.792+2212C>A		intron	N/A	NP_002471.1
	PPP1R12A	NM_001143885.2		c.792+2212C>A		intron	N/A	NP_001137357.1
	PPP1R12A	NM_001244990.2		c.792+2212C>A		intron	N/A	NP_001231919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12A	ENST00000450142.7	TSL:1 MANE Select	c.792+2212C>A		intron	N/A	ENSP00000389168.2
	PPP1R12A	ENST00000437004.6	TSL:1	c.792+2212C>A		intron	N/A	ENSP00000416769.2
	PPP1R12A	ENST00000550107.5	TSL:1	c.792+2212C>A		intron	N/A	ENSP00000446855.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54336 AN: 151482 Hom.: 17015 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54476 AN: 151602 Hom.: 17082 Cov.: 32 AF XY: 0.364 AC XY: 26964 AN XY: 74112

African (AFR) AF: 0.804 AC: 33293 AN: 41404

American (AMR) AF: 0.292 AC: 4442 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4060 AN: 5150

South Asian (SAS) AF: 0.451 AC: 2167 AN: 4810

European-Finnish (FIN) AF: 0.164 AC: 1709 AN: 10398

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7269 AN: 67840

Other (OTH) AF: 0.297 AC: 625 AN: 2102

Alfa AF: 0.261 Hom.: 1435

Bravo AF: 0.386

Asia WGS AF: 0.667 AC: 2297 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.47
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs10778691; hg19: chr12-80219888;