dbSNP rs17759843: PPM1F:c.*2720C>T (chr22-21920372-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014634.4(PPM1F):c.*2720C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 152,744 control chromosomes in the GnomAD database, including 443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 443 hom., cov: 33)

Exomes 𝑓: 0.052 ( 0 hom. )

Consequence

PPM1F
NM_014634.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.388

Publications

11 publications found

Variant links:

Genes affected

PPM1F (HGNC:19388): (protein phosphatase, Mg2+/Mn2+ dependent 1F) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PPM1F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1F	NM_014634.4 link	c.*2720C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000263212.10	NP_055449.1	P49593-1
PPM1F	NM_001410836.1 link	c.*2720C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001397765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1F	ENST00000263212.10 link	c.*2720C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_014634.4	ENSP00000263212.5		P49593-1
PPM1F	ENST00000407142.5 link	c.*2720C>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000384930.1		B5MCT7

Frequencies

GnomAD3 genomes

AF:

0.0660

AC:

10049

AN:

152186

Hom.:

444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0690

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0688

GnomAD4 exome

AF:

0.0523

AC:

AN:

440

Hom.:

Cov.:

AF XY:

0.0526

AC XY:

AN XY:

266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0513

AC:

AN:

390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0659

AC:

10044

AN:

152304

Hom.:

443

Cov.:

AF XY:

0.0627

AC XY:

4667

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0179

AC:

743

AN:

41574

American (AMR)

AF:

0.0688

AC:

1052

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0462

AC:

491

AN:

10624

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6816

AN:

68004

Other (OTH)

AF:

0.0681

AC:

144

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

471

943

1414

1886

2357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0908

Hom.:

1100

Bravo

AF:

0.0666

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.70

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over