12-79935464-T-G

Variant names:

• chr12-79935464-T-G
• rs3762111
• ENST00000552885.2:n.564T>G

Variant summary

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

The ENST00000552885.2(PPP1R12A-AS1):​n.564T>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 ENST00000552885.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 7 publications found

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]

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=-0.77).
• 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 rank	MANE	Protein	UniProt
PPP1R12A-AS1	NR_146533.1	n.184T>G		non_coding_transcript_exon_variant	Exon 1 of 3
PPP1R12A-AS1	NR_146534.1	n.184T>G		non_coding_transcript_exon_variant	Exon 1 of 2
PPP1R12A-AS1	NR_146535.1	n.184T>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12A-AS1	ENST00000552885.2	n.564T>G		non_coding_transcript_exon_variant	Exon 1 of 3	3
PPP1R12A-AS1	ENST00000798430.1	n.156T>G		non_coding_transcript_exon_variant	Exon 1 of 2
PPP1R12A-AS1	ENST00000798431.1	n.218T>G		non_coding_transcript_exon_variant	Exon 1 of 2

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

African (AFR) AF: 0.588 AC: 9327 AN: 15850

American (AMR) AF: 0.890 AC: 902 AN: 1014

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 4922 AN: 5206

East Asian (EAS) AF: 0.655 AC: 2394 AN: 3654

South Asian (SAS) AF: 0.793 AC: 13290 AN: 16754

European-Finnish (FIN) AF: 0.884 AC: 297 AN: 336

Middle Eastern (MID) AF: 0.876 AC: 1423 AN: 1624

European-Non Finnish (NFE) AF: 0.927 AC: 706955 AN: 762808

Other (OTH) AF: 0.886 AC: 24256 AN: 27372

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

African (AFR) AF: 0.606 AC: 25179 AN: 41520

American (AMR) AF: 0.876 AC: 13404 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3271 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3434 AN: 5152

South Asian (SAS) AF: 0.777 AC: 3752 AN: 4830

European-Finnish (FIN) AF: 0.875 AC: 9275 AN: 10604

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62924 AN: 68032

Other (OTH) AF: 0.851 AC: 1799 AN: 2114

Alfa AF: 0.848 Hom.: 8447

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
PhyloP100		0.39
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3762111; hg19: chr12-80329244;