Variant 3-52247772-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144641.4(PPM1M):c.688A>G(p.Met230Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,342,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

PPM1M
NM_144641.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.53

Variant links:

Genes affected

PPM1M (HGNC:26506): (protein phosphatase, Mg2+/Mn2+ dependent 1M) Predicted to enable manganese ion binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PPM1M links:

PPM1M (HGNC:):

PPM1M links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039471626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1M	NM_144641.4 linkuse as main transcript	c.688A>G	p.Met230Val	missense_variant	4/10	ENST00000323588.9	NP_653242.3	Q96MI6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1M	ENST00000323588.9 linkuse as main transcript	c.688A>G	p.Met230Val	missense_variant	4/10	1	NM_144641.4	ENSP00000319894.5		Q96MI6-5

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

141920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000497

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000856

AC:

AN:

233734

Hom.:

AF XY:

0.00000793

AC XY:

AN XY:

126148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000333

AC:

AN:

1200136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

594376

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000425

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000141

AC:

AN:

142072

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

69026

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000497

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.012

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.6

.;N;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

2.1

.;N;N

REVEL

Benign

0.16

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.23

MutPred

0.51

Gain of catalytic residue at M230 (P = 0.0385);.;.;

MVP

0.081

MPC

0.21

ClinPred

0.022

GERP RS

2.2

Varity_R

0.044

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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