Variant chr17-58756340-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014906.5(PPM1E):c.343C>T(p.Pro115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,221,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000016 ( 0 hom. )

Consequence

PPM1E
NM_014906.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

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:

PPM1E (HGNC:):

PPM1E links:

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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=0.114647955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1E	NM_014906.5 linkuse as main transcript	c.343C>T	p.Pro115Ser	missense_variant	1/7	ENST00000308249.4	NP_055721.3	Q8WY54-2
PPM1E	NR_048561.1 linkuse as main transcript	n.472C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1E	ENST00000308249.4 linkuse as main transcript	c.343C>T	p.Pro115Ser	missense_variant	1/7	1	NM_014906.5	ENSP00000312411.2		Q8WY54-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000164

AC:

AN:

1221226

Hom.:

Cov.:

AF XY:

0.00000168

AC XY:

AN XY:

594614

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:

0.00000200

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

May 08, 2024

The c.343C>T (p.P115S) alteration is located in exon 1 (coding exon 1) of the PPM1E gene. This alteration results from a C to T substitution at nucleotide position 343, causing the proline (P) at amino acid position 115 to be replaced by a serine (S). 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

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.18

REVEL

Benign

0.032

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.031

Vest4

0.19

MutPred

0.19

Loss of catalytic residue at P115 (P = 0.0059);

MVP

0.043

MPC

1.1

ClinPred

0.37

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.31

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