dbSNP rs975574946: PPM1E:p.Pro118Ser (chr17-58756349-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014906.5(PPM1E):c.352C>T(p.Pro118Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,380,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

PPM1E
NM_014906.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1367009).

BS2

High AC in GnomAd4 at 23 AD gene.

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.352C>T	p.Pro118Ser	missense	Exon 1 of 7	NP_055721.3
	PPM1E	NR_048561.1		n.481C>T		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.352C>T	p.Pro118Ser	missense	Exon 1 of 7	ENSP00000312411.2	Q8WY54-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000814

AC:

AN:

1228866

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

599174

show subpopulations

African (AFR)

AF:

0.000379

AC:

AN:

23722

American (AMR)

AF:

0.0000868

AC:

AN:

11516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16778

East Asian (EAS)

AF:

0.00

AC:

AN:

27748

South Asian (SAS)

AF:

0.00

AC:

AN:

50138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1002896

Other (OTH)

AF:

0.00

AC:

AN:

49978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

4.2

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.47

REVEL

Benign

0.059

Sift

Uncertain

0.0040

Sift4G

Benign

0.16

Vest4

0.32

MVP

0.043

MPC

1.1

ClinPred

0.69

GERP RS

2.3

PromoterAI

-0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.083

gMVP

0.094

Mutation Taster

=94/6

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over