Variant 22-21923294-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014634.4(PPM1F):c.1163G>A(p.Arg388His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PPM1F
NM_014634.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

PPM1F (HGNC:19388): (protein phosphatase, Mg2+/Mn2+ dependent 1F) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PPM1F links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01225853).

BP6

Variant 22-21923294-C-T is Benign according to our data. Variant chr22-21923294-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2692829.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1F	NM_014634.4 linkuse as main transcript	c.1163G>A	p.Arg388His	missense_variant	8/8	ENST00000263212.10	NP_055449.1
PPM1F	NM_001410836.1 linkuse as main transcript	c.659G>A	p.Arg220His	missense_variant	7/7		NP_001397765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1F	ENST00000263212.10 linkuse as main transcript	c.1163G>A	p.Arg388His	missense_variant	8/8	1	NM_014634.4	ENSP00000263212	P1	P49593-1
PPM1F	ENST00000407142.5 linkuse as main transcript	c.659G>A	p.Arg220His	missense_variant	6/6	5		ENSP00000384930
PPM1F	ENST00000496143.5 linkuse as main transcript	n.375G>A		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000225

AC:

AN:

249030

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.00242

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000626

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1461172

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000814

AC:

124

AN:

152284

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000907

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Labcorp Genetics (formerly Invitae), Labcorp

Nov 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.84

DANN

Benign

0.81

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.070

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.014

Sift

Benign

0.28

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0010

B;.

Vest4

0.035

MVP

0.10

MPC

0.50

ClinPred

0.0022

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over