Variant chr22-21939548-TTCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_014634.4(PPM1F):c.336_338del(p.Glu113del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,591,094 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 42 hom. )

Consequence

PPM1F
NM_014634.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.553

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:

PPM1F-AS1 (HGNC:40888): (PPM1F antisense RNA 1)

PPM1F-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_014634.4

BP6

Variant 22-21939548-TTCC-T is Benign according to our data. Variant chr22-21939548-TTCC-T is described in ClinVar as [Benign]. Clinvar id is 2038201.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPM1F	NM_014634.4 linkuse as main transcript	c.336_338del	p.Glu113del	inframe_deletion	3/8	ENST00000263212.10	NP_055449.1
PPM1F-AS1	NR_147620.1 linkuse as main transcript	n.1318_1320del		non_coding_transcript_exon_variant	1/2
PPM1F	NM_001410836.1 linkuse as main transcript	c.-169_-167del		5_prime_UTR_variant	2/7		NP_001397765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1F	ENST00000263212.10 linkuse as main transcript	c.336_338del	p.Glu113del	inframe_deletion	3/8	1	NM_014634.4	ENSP00000263212	P1	P49593-1
PPM1F-AS1	ENST00000458178.2 linkuse as main transcript	n.1262_1264del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.00361

AC:

549

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00450

AC:

947

AN:

210624

Hom.:

AF XY:

0.00522

AC XY:

589

AN XY:

112818

show subpopulations

Gnomad AFR exome

AF:

0.000611

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00442

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.00159

Gnomad NFE exome

AF:

0.00517

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00463

AC:

6665

AN:

1438768

Hom.:

AF XY:

0.00487

AC XY:

3473

AN XY:

713306

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.00276

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00474

Gnomad4 OTH exome

AF:

0.00396

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152326

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00458

Hom.:

Bravo

AF:

0.00346

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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