GeneBe

chr12-79935464-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.388

Publications

0 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

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-AS1NR_146533.1 linkn.184T>A non_coding_transcript_exon_variant Exon 1 of 3
PPP1R12A-AS1NR_146534.1 linkn.184T>A non_coding_transcript_exon_variant Exon 1 of 2
PPP1R12A-AS1NR_146535.1 linkn.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-AS1ENST00000552885.2 linkn.564T>A non_coding_transcript_exon_variant Exon 1 of 3 3
PPP1R12A-AS1ENST00000798430.1 linkn.156T>A non_coding_transcript_exon_variant Exon 1 of 2
PPP1R12A-AS1ENST00000798431.1 linkn.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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Publications

Other links and lift over

dbSNP: rs3762111; hg19: chr12-80329244; API