rs3762111

Positions:

• chr12-79935464-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_146533.1(PPP1R12A-AS1):​n.184T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 986,844 control chromosomes in the GnomAD database, including 402,889 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 0.82 (52097 hom., cov: 34)
  • Exomes 𝑓: 0.92 (350792 hom.)
• Consequence: PPP1R12A-AS1 NR_146533.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

PPP1R12A-AS1 (HGNC:51903): (PPP1R12A antisense RNA 1)

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R12A-AS1	NR_146533.1	n.184T>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R12A-AS1	ENST00000552885.2	n.564T>G		non_coding_transcript_exon_variant	1/3	3
PPP1R12A	ENST00000437004.6			upstream_gene_variant		1
PPP1R12A	ENST00000261207.9			upstream_gene_variant		5		P3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124099 AN: 152108 Hom.: 52089 Cov.: 34

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.915 AC: 763766 AN: 834618 Hom.: 350792 Cov.: 49 AF XY: 0.915 AC XY: 352862 AN XY: 385550

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.890

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.816 AC: 124148 AN: 152226 Hom.: 52097 Cov.: 34 AF XY: 0.814 AC XY: 60588 AN XY: 74432

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.851

Alfa AF: 0.857 Hom.: 8306

Bravo AF: 0.808

Asia WGS AF: 0.678 AC: 2359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762111; hg19: chr12-80329244;