rs116564150

chr4-88278245-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152542.5(PPM1K):c.339C>T(p.Phe113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00999 in 1,614,138 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (9 hom., cov: 33)
  • Exomes 𝑓: 0.010 (102 hom.)
• Consequence: PPM1K NM_152542.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.48

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-88278245-G-A is Benign according to our data. Variant chr4-88278245-G-A is described in ClinVar as [Benign]. Clinvar id is 473874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.48 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1K	NM_152542.5	c.339C>T	p.Phe113=	synonymous_variant	2/7	ENST00000608933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1K	ENST00000608933.6	c.339C>T	p.Phe113=	synonymous_variant	2/7	1	NM_152542.5	P1

Frequencies

GnomAD3 genomes AF: 0.00750 AC: 1142 AN: 152174 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00769 AC: 1933 AN: 251350 Hom.: 15 AF XY: 0.00806 AC XY: 1095 AN XY: 135842

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00797

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.0102 AC: 14983 AN: 1461846 Hom.: 102 Cov.: 31 AF XY: 0.0101 AC XY: 7339 AN XY: 727220

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00403

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00831

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.00960

GnomAD4 genome AF: 0.00749 AC: 1141 AN: 152292 Hom.: 9 Cov.: 33 AF XY: 0.00766 AC XY: 570 AN XY: 74460

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00856 Hom.: 5

Bravo AF: 0.00657

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00883

EpiControl AF: 0.00961

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maple syrup urine disease, mild variant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.8
Dann	Benign	0.87

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: rs116564150; hg19: chr4-89199397;