rs3762111

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-79935464-T-A
• chr12-79935464-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000552885.2(PPP1R12A-AS1):​n.564T>A 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 0.0000012 in 834,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: PPP1R12A-AS1 ENST00000552885.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12A-AS1	NR_146533.1	n.184T>A		non_coding_transcript_exon_variant	Exon 1 of 3
PPP1R12A-AS1	NR_146534.1	n.184T>A		non_coding_transcript_exon_variant	Exon 1 of 2
PPP1R12A-AS1	NR_146535.1	n.184T>A		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>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
PPP1R12A-AS1	ENST00000798430.1	n.156T>A		non_coding_transcript_exon_variant	Exon 1 of 2
PPP1R12A-AS1	ENST00000798431.1	n.218T>A		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 834620 Hom.: 0 Cov.: 49 AF XY: 0.00 AC XY: 0 AN XY: 385550

African (AFR) AF: 0.00 AC: 0 AN: 15852

American (AMR) AF: 0.00 AC: 0 AN: 1014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5206

East Asian (EAS) AF: 0.00 AC: 0 AN: 3654

South Asian (SAS) AF: 0.00 AC: 0 AN: 16754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 762808

Other (OTH) AF: 0.00 AC: 0 AN: 27372

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.1
DANN	Benign	0.36
PhyloP100		0.39
PromoterAI		-0.039	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;