Variant chr11-74222316-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016147.3(PPME1):c.293C>A(p.Ala98Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPME1
NM_016147.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Variant links:

Genes affected

PPME1 (HGNC:30178): (protein phosphatase methylesterase 1) This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

PPME1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28328583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPME1	NM_016147.3 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/14	ENST00000328257.13
PPME1	NM_001271593.2 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/14
PPME1	XM_047427116.1 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/12
PPME1	XM_017017913.3 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPME1	ENST00000328257.13 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/14	1	NM_016147.3	P1	Q9Y570-1
PPME1	ENST00000398427.6 linkuse as main transcript	c.293C>A	p.Ala98Glu	missense_variant	4/14	1			Q9Y570-4
PPME1	ENST00000544401.2 linkuse as main transcript	n.372C>A		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248640

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457624

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725348

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.293C>A (p.A98E) alteration is located in exon 4 (coding exon 4) of the PPME1 gene. This alteration results from a C to A substitution at nucleotide position 293, causing the alanine (A) at amino acid position 98 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.036

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.060

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.17

Sift

Benign

0.89

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0080

B;.

Vest4

0.60

MutPred

0.52

Loss of MoRF binding (P = 0.0648);Loss of MoRF binding (P = 0.0648);

MVP

0.38

MPC

0.59

ClinPred

0.53

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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