chr1-202442551-A-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002481.4(PPP1R12B):c.1646A>G(p.Tyr549Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000451 in 1,612,818 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 4 hom. )
Consequence
PPP1R12B
NM_002481.4 missense
NM_002481.4 missense
Scores
1
4
10
Clinical Significance
Conservation
PhyloP100: 2.51
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008294284).
BP6
?
Variant 1-202442551-A-G is Benign according to our data. Variant chr1-202442551-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639789.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 383 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP1R12B | NM_002481.4 | c.1646A>G | p.Tyr549Cys | missense_variant | 12/24 | ENST00000608999.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP1R12B | ENST00000608999.6 | c.1646A>G | p.Tyr549Cys | missense_variant | 12/24 | 1 | NM_002481.4 | A2 | |
PPP1R12B | ENST00000391959.5 | c.1646A>G | p.Tyr549Cys | missense_variant | 12/25 | 5 | P3 | ||
PPP1R12B | ENST00000704899.1 | c.1646A>G | p.Tyr549Cys | missense_variant | 12/24 | ||||
PPP1R12B | ENST00000434615.2 | c.26A>G | p.Tyr9Cys | missense_variant, NMD_transcript_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00252 AC: 383AN: 151960Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000667 AC: 167AN: 250342Hom.: 0 AF XY: 0.000495 AC XY: 67AN XY: 135330
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GnomAD4 exome AF: 0.000236 AC: 345AN: 1460746Hom.: 4 Cov.: 30 AF XY: 0.000202 AC XY: 147AN XY: 726702
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GnomAD4 genome ? AF: 0.00252 AC: 383AN: 152072Hom.: 3 Cov.: 32 AF XY: 0.00233 AC XY: 173AN XY: 74264
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | PPP1R12B: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
0.0070
.;B
Vest4
MVP
0.51
MPC
0.21
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at