Genetic Variant PPM1E:p.Pro122Leu (chr17-58756362-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014906.5(PPM1E):c.365C>T(p.Pro122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,376,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P122Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

PPM1E
NM_014906.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

PPM1E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23609492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1E	NM_014906.5 link	c.365C>T	p.Pro122Leu	missense_variant	Exon 1 of 7	ENST00000308249.4	NP_055721.3	Q8WY54-2
PPM1E	NR_048561.1 link	n.494C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1E	ENST00000308249.4 link	c.365C>T	p.Pro122Leu	missense_variant	Exon 1 of 7	1	NM_014906.5	ENSP00000312411.2		Q8WY54-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000245

AC:

AN:

1224880

Hom.:

Cov.:

AF XY:

0.00000335

AC XY:

AN XY:

596936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000421

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000204

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0041

Eigen

Benign

0.12

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.18

REVEL

Benign

0.082

Sift

Benign

0.48

Sift4G

Benign

0.20

Vest4

0.42

MutPred

0.22

Loss of glycosylation at P122 (P = 0.004);

MVP

0.21

MPC

1.1

ClinPred

0.15

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.078

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over