rs34981823

chr4-88265010-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_152542.5(PPM1K):c.978G>A(p.Val326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,613,966 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (132 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (121 hom.)
• Consequence: PPM1K NM_152542.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399

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 -16 ACMG points.

• BP6: Variant 4-88265010-C-T is Benign according to our data. Variant chr4-88265010-C-T is described in ClinVar as [Benign]. Clinvar id is 473876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1K	NM_152542.5	c.978G>A	p.Val326=	synonymous_variant	6/7	ENST00000608933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1K	ENST00000608933.6	c.978G>A	p.Val326=	synonymous_variant	6/7	1	NM_152542.5	P1
PPM1K	ENST00000508256.5	c.321G>A	p.Val107=	synonymous_variant	5/6	2
PPM1K	ENST00000295908.11	c.853-2284G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3480 AN: 152136 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00983

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.0210

GnomAD3 exomes AF: 0.00671 AC: 1686 AN: 251288 Hom.: 52 AF XY: 0.00495 AC XY: 673 AN XY: 135834

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.00754

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00273 AC: 3990 AN: 1461712 Hom.: 121 Cov.: 31 AF XY: 0.00244 AC XY: 1776 AN XY: 727164

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.00559

Gnomad4 ASJ exome AF: 0.00792

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.00679

GnomAD4 genome AF: 0.0229 AC: 3485 AN: 152254 Hom.: 132 Cov.: 33 AF XY: 0.0227 AC XY: 1689 AN XY: 74436

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.00975

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0122 Hom.: 49

Bravo AF: 0.0262

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000764

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PPM1K-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Maple syrup urine disease, mild variant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.39		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34981823; hg19: chr4-89186162;