rs551955938

Variant names:

• chr22-21939548-TTCC-T
• rs551955938
• NM_014634.4:c.336_338delGGA

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_014634.4(PPM1F):​c.336_338delGGA​(p.Glu113del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.553
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2038201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 42 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014634.4. 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
	PPM1F	NM_014634.4	MANE Select	c.336_338delGGA	p.Glu113del	disruptive_inframe_deletion	Exon 3 of 8	NP_055449.1	P49593-1
	PPM1F	NM_001410836.1		c.-169_-167delGGA		5_prime_UTR	Exon 2 of 7	NP_001397765.1	B5MCT7
	PPM1F-AS1	NR_147620.1		n.1318_1320delCTC		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1F	ENST00000263212.10	TSL:1 MANE Select	c.336_338delGGA	p.Glu113del	disruptive_inframe_deletion	Exon 3 of 8	ENSP00000263212.5	P49593-1
	PPM1F-AS1	ENST00000458178.2	TSL:1	n.1262_1264delCTC		non_coding_transcript_exon	Exon 1 of 2
	PPM1F	ENST00000397495.8	TSL:2	c.336_338delGGA	p.Glu113del	disruptive_inframe_deletion	Exon 3 of 7	ENSP00000380632.4	A8MX49

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 549 AN: 152208 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00450 AC: 947 AN: 210624 AF XY: 0.00522

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 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.: 42 AF XY: 0.00487 AC XY: 3473 AN XY: 713306

African (AFR) AF: 0.000602 AC: 20 AN: 33198

American (AMR) AF: 0.00276 AC: 113 AN: 40876

Ashkenazi Jewish (ASJ) AF: 0.00429 AC: 110 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 39092

South Asian (SAS) AF: 0.0101 AC: 837 AN: 83096

European-Finnish (FIN) AF: 0.00133 AC: 69 AN: 51900

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5740

European-Non Finnish (NFE) AF: 0.00474 AC: 5216 AN: 1099606

Other (OTH) AF: 0.00396 AC: 236 AN: 59596

GnomAD4 genome AF: 0.00359 AC: 547 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.00353 AC XY: 263 AN XY: 74480

African (AFR) AF: 0.000842 AC: 35 AN: 41576

American (AMR) AF: 0.00314 AC: 48 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00544 AC: 370 AN: 68022

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00458 Hom.: 0

Bravo AF: 0.00346

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs551955938; hg19: chr22-22293920;