Genetic Variant NM_014906.5:c.344C>A (chr17-58756341-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014906.5(PPM1E):c.344C>A(p.Pro115Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. P115S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPM1E
NM_014906.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.717

Publications

0 publications found

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:

LOC105371843 (HGNC:):

LOC105371843 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19857863).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014906.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	NM_014906.5	MANE Select	c.344C>A	p.Pro115Gln	missense	Exon 1 of 7	NP_055721.3
	PPM1E	NR_048561.1		n.473C>A		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	ENST00000308249.4	TSL:1 MANE Select	c.344C>A	p.Pro115Gln	missense	Exon 1 of 7	ENSP00000312411.2	Q8WY54-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1220244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

594126

African (AFR)

AF:

0.00

AC:

AN:

23692

American (AMR)

AF:

0.00

AC:

AN:

11442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16636

East Asian (EAS)

AF:

0.00

AC:

AN:

27648

South Asian (SAS)

AF:

0.00

AC:

AN:

48250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3338

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

997940

Other (OTH)

AF:

0.00

AC:

AN:

49560

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.063

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.72

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.53

REVEL

Benign

0.079

Sift

Uncertain

0.0030

Sift4G

Benign

0.096

Vest4

0.29

MutPred

0.20

Loss of glycosylation at P115 (P = 0.0071)

MVP

0.043

MPC

0.97

ClinPred

0.66

GERP RS

3.4

PromoterAI

-0.053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.093

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over