14-60282400-G-C

Variant names:

• chr14-60282400-G-C
• rs7154773
• NM_021003.5:c.-20-284G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021003.5(PPM1A):​c.-20-284G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,022 control chromosomes in the GnomAD database, including 17,953 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 0.45 (17953 hom., cov: 32)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021003.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1A	NM_021003.5	MANE Select	c.-20-284G>C		intron	N/A	NP_066283.1
	PPM1A	NM_177952.3		c.200-284G>C		intron	N/A	NP_808821.2
	PPM1A	NM_177951.3		c.-20-284G>C		intron	N/A	NP_808820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1A	ENST00000395076.9	TSL:1 MANE Select	c.-20-284G>C		intron	N/A	ENSP00000378514.4
	PPM1A	ENST00000325658.3	TSL:1	c.-20-284G>C		intron	N/A	ENSP00000314850.3
	PPM1A	ENST00000531143.6	TSL:1	n.*5-284G>C		intron	N/A	ENSP00000437200.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67936 AN: 151902 Hom.: 17910 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.448 AC: 68030 AN: 152022 Hom.: 17953 Cov.: 32 AF XY: 0.440 AC XY: 32683 AN XY: 74318

African (AFR) AF: 0.742 AC: 30748 AN: 41444

American (AMR) AF: 0.333 AC: 5085 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3470

East Asian (EAS) AF: 0.130 AC: 671 AN: 5166

South Asian (SAS) AF: 0.457 AC: 2201 AN: 4816

European-Finnish (FIN) AF: 0.276 AC: 2914 AN: 10556

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23525 AN: 67978

Other (OTH) AF: 0.432 AC: 912 AN: 2110

Alfa AF: 0.239 Hom.: 595

Bravo AF: 0.462

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.089
DANN	Benign	0.39
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7154773; hg19: chr14-60749118;