rs17097262

Variant names:

• chr14-60271639-C-T
• rs17097262
• NM_021003.5:c.-20-11045C>T

Variant summary

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

The NM_021003.5(PPM1A):​c.-20-11045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,158 control chromosomes in the GnomAD database, including 724 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 0.075 (724 hom., cov: 32)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.-20-11045C>T		intron	N/A	NP_066283.1
	PPM1A	NM_177952.3		c.200-11045C>T		intron	N/A	NP_808821.2
	PPM1A	NM_177951.3		c.-20-11045C>T		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.-20-11045C>T		intron	N/A	ENSP00000378514.4
	PPM1A	ENST00000325658.3	TSL:1	c.-20-11045C>T		intron	N/A	ENSP00000314850.3
	PPM1A	ENST00000531143.6	TSL:1	n.200-5366C>T		intron	N/A	ENSP00000437200.2

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11449 AN: 152040 Hom.: 726 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0753 AC: 11453 AN: 152158 Hom.: 724 Cov.: 32 AF XY: 0.0730 AC XY: 5431 AN XY: 74392

African (AFR) AF: 0.179 AC: 7433 AN: 41500

American (AMR) AF: 0.0543 AC: 831 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4814

European-Finnish (FIN) AF: 0.0126 AC: 134 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0374 AC: 2540 AN: 67986

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0572 Hom.: 231

Bravo AF: 0.0844

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.80
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17097262; hg19: chr14-60738357;