Variant 17-58756130-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014906.5(PPM1E):c.133T>C(p.Ser45Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 86,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPM1E
NM_014906.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00700

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065124333).

BS2

High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPM1E	NM_014906.5 linkuse as main transcript	c.133T>C	p.Ser45Pro	missense_variant	1/7	ENST00000308249.4
PPM1E	NR_048561.1 linkuse as main transcript	n.262T>C		non_coding_transcript_exon_variant	1/6
LOC105371843	XR_007065866.1 linkuse as main transcript			upstream_gene_variant
LOC105371843	XR_007065865.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1E	ENST00000308249.4 linkuse as main transcript	c.133T>C	p.Ser45Pro	missense_variant	1/7	1	NM_014906.5	P1	Q8WY54-2

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

86596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

220882

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

120168

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.0000940

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000935

Gnomad OTH exome

AF:

0.000363

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000704

AC:

AN:

667974

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

340604

show subpopulations

Gnomad4 AFR exome

AF:

0.000771

Gnomad4 AMR exome

AF:

0.000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000334

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.0000837

Gnomad4 NFE exome

AF:

0.0000379

Gnomad4 OTH exome

AF:

0.0000326

GnomAD4 genome

AF:

0.000115

AC:

AN:

86660

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

42252

show subpopulations

Gnomad4 AFR

AF:

0.000430

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000455

Hom.:

ExAC

AF:

0.000224

AC:

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

Aug 09, 2021

The c.133T>C (p.S45P) alteration is located in exon 1 (coding exon 1) of the PPM1E gene. This alteration results from a T to C substitution at nucleotide position 133, causing the serine (S) at amino acid position 45 to be replaced by a proline (P). 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

0.053

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

Cadd

Benign

3.1

Dann

Benign

0.28

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.14

REVEL

Benign

0.017

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.22

MVP

0.068

MPC

1.3

ClinPred

0.0021

GERP RS

-1.3

Varity_R

0.046

gMVP

0.070

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