chr12-79935553-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2643190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 25 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_146535.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12A-AS1	NR_146533.1		n.273A>C		non_coding_transcript_exon	Exon 1 of 3
	PPP1R12A-AS1	NR_146534.1		n.273A>C		non_coding_transcript_exon	Exon 1 of 2
	PPP1R12A-AS1	NR_146535.1		n.273A>C		splice_region non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12A-AS1	ENST00000552885.2	TSL:3	n.653A>C		non_coding_transcript_exon	Exon 1 of 3
	PPP1R12A-AS1	ENST00000798430.1		n.245A>C		non_coding_transcript_exon	Exon 1 of 2
	PPP1R12A-AS1	ENST00000798431.1		n.307A>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.00127 AC: 20 AN: 15792

American (AMR) AF: 0.00606 AC: 6 AN: 990

Ashkenazi Jewish (ASJ) AF: 0.00775 AC: 40 AN: 5160

East Asian (EAS) AF: 0.00 AC: 0 AN: 3638

South Asian (SAS) AF: 0.000181 AC: 3 AN: 16564

European-Finnish (FIN) AF: 0.0310 AC: 9 AN: 290

Middle Eastern (MID) AF: 0.00185 AC: 3 AN: 1622

European-Non Finnish (NFE) AF: 0.00944 AC: 7198 AN: 762112

Other (OTH) AF: 0.00688 AC: 188 AN: 27318

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

African (AFR) AF: 0.00149 AC: 62 AN: 41560

American (AMR) AF: 0.00360 AC: 55 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.0563 AC: 597 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 792 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.0106 Hom.: 13

Bravo AF: 0.00575

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.11
PromoterAI		-0.021	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs76824425; hg19: chr12-80329333;