rs17759843

Positions:

• chr22-21920372-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PPM1F	NM_014634.4	c.*2720C>T		3_prime_UTR_variant	8/8	ENST00000263212.10	NP_055449.1
PPM1F	NM_001410836.1	c.*2720C>T		3_prime_UTR_variant	7/7		NP_001397765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1F	ENST00000263212.10	c.*2720C>T		3_prime_UTR_variant	8/8	1	NM_014634.4	ENSP00000263212	P1
PPM1F	ENST00000407142.5	c.*2720C>T		3_prime_UTR_variant	6/6	5		ENSP00000384930

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10049 AN: 152186 Hom.: 444 Cov.: 33

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: 23 AN: 440 Hom.: 0 Cov.: 0 AF XY: 0.0526 AC XY: 14 AN XY: 266

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0659 AC: 10044 AN: 152304 Hom.: 443 Cov.: 33 AF XY: 0.0627 AC XY: 4667 AN XY: 74472

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0938 Hom.: 916

Bravo AF: 0.0666

Asia WGS AF: 0.0110 AC: 39 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
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs17759843; hg19: chr22-22274745;