dbSNP rs2843414: PPP1R12B:p.Val182Ile (chr1-202425568-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000608999.6(PPP1R12B):c.544G>A(p.Val182Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V182A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PPP1R12B
ENST00000608999.6 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

1 publications found

Variant links:

Genes affected

PPP1R12B (HGNC:7619): (protein phosphatase 1 regulatory subunit 12B) Myosin phosphatase is a protein complex comprised of three subunits: a catalytic subunit (PP1c-delta, protein phosphatase 1, catalytic subunit delta), a large regulatory subunit (MYPT, myosin phosphatase target) and small regulatory subunit (sm-M20). Two isoforms of MYPT have been isolated--MYPT1 and MYPT2, the first of which is widely expressed, and the second of which may be specific to heart, skeletal muscle, and brain. Each of the MYPT isoforms functions to bind PP1c-delta and increase phosphatase activity. This locus encodes both MYTP2 and M20. Alternatively spliced transcript variants encoding different isoforms have been identified. Related pseudogenes have been defined on the Y chromosome. [provided by RefSeq, Oct 2011]

PPP1R12B links:

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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 (MetaRNN=0.029557526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000608999.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PPP1R12B	NM_002481.4	MANE Select	c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 24	NP_002472.2
PPP1R12B	NM_001331029.2		c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 25	NP_001317958.1
PPP1R12B	NM_001410283.1		c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 25	NP_001397212.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PPP1R12B	ENST00000608999.6	TSL:1 MANE Select	c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 24	ENSP00000476755.1
PPP1R12B	ENST00000480184.5	TSL:1	c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 10	ENSP00000417159.1
PPP1R12B	ENST00000356764.6	TSL:1	c.544G>A	p.Val182Ile	missense splice_region	Exon 4 of 9	ENSP00000349206.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.044

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.015

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.24

PhyloP100

2.5

PrimateAI

Benign

0.32

PROVEAN

Benign

0.0

REVEL

Benign

0.073

Sift

Benign

0.51

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.16

MutPred

0.073

Gain of helix (P = 0.0854)

MVP

0.39

MPC

0.13

ClinPred

0.25

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.18

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over