rs893971

chr4-88282518-A-Gchr4-88282518-A-T

Variant summary

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

The NM_152542.5(PPM1K):c.-60+1888T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,154 control chromosomes in the GnomAD database, including 8,702 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 0.32 (8702 hom., cov: 33)
• Consequence: PPM1K NM_152542.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

Genes affected

PPM1K (HGNC:25415): (protein phosphatase, Mg2+/Mn2+ dependent 1K) This gene encodes a member of the PPM family of Mn2+/Mg2+-dependent protein phosphatases. The encoded protein, essential for cell survival and development, is targeted to the mitochondria where it plays a key role in regulation of the mitochondrial permeability transition pore. [provided by RefSeq, Sep 2012]

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 = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1K	NM_152542.5	c.-60+1888T>C		intron_variant		ENST00000608933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1K	ENST00000608933.6	c.-60+1888T>C		intron_variant		1	NM_152542.5	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48857 AN: 152036 Hom.: 8700 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48872 AN: 152154 Hom.: 8702 Cov.: 33 AF XY: 0.316 AC XY: 23512 AN XY: 74382

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.0146

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.332

Alfa AF: 0.375 Hom.: 13730

Bravo AF: 0.308

Asia WGS AF: 0.137 AC: 478 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.6
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs893971; hg19: chr4-89203670;