NM_002480.3:c.2001-2958C>T

Variant names:

• chr12-79801542-G-A
• rs7957959
• NM_002480.3:c.2001-2958C>T

Variant summary

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

The NM_002480.3(PPP1R12A):​c.2001-2958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 151,806 control chromosomes in the GnomAD database, including 67,104 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 0.94 (67104 hom., cov: 28)
• Consequence: PPP1R12A NM_002480.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12A	NM_002480.3	c.2001-2958C>T		intron_variant	Intron 14 of 24	ENST00000450142.7	NP_002471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12A	ENST00000450142.7	c.2001-2958C>T		intron_variant	Intron 14 of 24	1	NM_002480.3	ENSP00000389168.2

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142316 AN: 151690 Hom.: 67057 Cov.: 28

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.938 AC: 142418 AN: 151806 Hom.: 67104 Cov.: 28 AF XY: 0.932 AC XY: 69174 AN XY: 74182

African (AFR) AF: 0.986 AC: 40874 AN: 41468

American (AMR) AF: 0.938 AC: 14288 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3358 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3625 AN: 5138

South Asian (SAS) AF: 0.819 AC: 3933 AN: 4800

European-Finnish (FIN) AF: 0.884 AC: 9231 AN: 10446

Middle Eastern (MID) AF: 0.952 AC: 278 AN: 292

European-Non Finnish (NFE) AF: 0.942 AC: 64000 AN: 67948

Other (OTH) AF: 0.943 AC: 1981 AN: 2100

Alfa AF: 0.946 Hom.: 23240

Bravo AF: 0.946

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.36
PhyloP100		-0.28
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: rs7957959; hg19: chr12-80195322;