12-79935553-A-C

Variant names:

• chr12-79935553-A-C
• rs76824425
• ENST00000552885.2:n.653A>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NR_146535.1(PPP1R12A-AS1):​n.273A>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 985,758 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (25 hom., cov: 33)
  • Exomes 𝑓: 0.0090 (31 hom.)
• Consequence: PPP1R12A-AS1 NR_146535.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-79935553-A-C is Benign according to our data. Variant chr12-79935553-A-C is described in ClinVar as [Benign]. Clinvar id is 2643190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12A-AS1	NR_146533.1	n.273A>C		non_coding_transcript_exon_variant	Exon 1 of 3
PPP1R12A-AS1	NR_146534.1	n.273A>C		non_coding_transcript_exon_variant	Exon 1 of 2
PPP1R12A-AS1	NR_146535.1	n.273A>C		splice_region_variant, 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.653A>C		non_coding_transcript_exon_variant	Exon 1 of 3	3
PPP1R12A	ENST00000437004.6	c.-221T>G		upstream_gene_variant		1		ENSP00000416769.2
PPP1R12A	ENST00000261207.9	c.-221T>G		upstream_gene_variant		5		ENSP00000261207.5

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1545 AN: 152154 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00896 AC: 7467 AN: 833486 Hom.: 31 Cov.: 31 AF XY: 0.00888 AC XY: 3417 AN XY: 384986

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.00775

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000181

Gnomad4 FIN exome AF: 0.0310

Gnomad4 NFE exome AF: 0.00944

Gnomad4 OTH exome AF: 0.00688

GnomAD4 genome AF: 0.0101 AC: 1545 AN: 152272 Hom.: 25 Cov.: 33 AF XY: 0.0118 AC XY: 881 AN XY: 74464

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.0122 Hom.: 1

Bravo AF: 0.00575

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPP1R12A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76824425; hg19: chr12-80329333;