rs12323784

chr14-60282062-G-A

Variant summary

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

The NM_021003.5(PPM1A):c.-20-622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,172 control chromosomes in the GnomAD database, including 614 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 0.071 (614 hom., cov: 32)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

Genes affected

PPM1A (HGNC:9275): (protein phosphatase, Mg2+/Mn2+ dependent 1A) 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 dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1A	NM_021003.5	c.-20-622G>A		intron_variant		ENST00000395076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1A	ENST00000395076.9	c.-20-622G>A		intron_variant		1	NM_021003.5	P1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10815 AN: 152054 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0711 AC: 10817 AN: 152172 Hom.: 614 Cov.: 32 AF XY: 0.0692 AC XY: 5147 AN XY: 74410

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0563 Hom.: 64

Bravo AF: 0.0796

Asia WGS AF: 0.0180 AC: 63 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12323784; hg19: chr14-60748780;