rs10130695

Variant names:

• chr14-60289266-C-T
• rs10130695
• NM_021003.5:c.953-540C>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.953-540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 151,974 control chromosomes in the GnomAD database, including 620 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 (620 hom., cov: 32)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1A	NM_021003.5	c.953-540C>T		intron_variant	Intron 3 of 5	ENST00000395076.9	NP_066283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1A	ENST00000395076.9	c.953-540C>T		intron_variant	Intron 3 of 5	1	NM_021003.5	ENSP00000378514.4
PPM1A	ENST00000531143.6	n.*977-540C>T		intron_variant	Intron 4 of 6	1		ENSP00000437200.2
PPM1A	ENST00000325642.7	c.1172-540C>T		intron_variant	Intron 3 of 5	2		ENSP00000327255.3
PPM1A	ENST00000532036.2	n.429-540C>T		intron_variant	Intron 3 of 5	5		ENSP00000436445.2

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10818 AN: 151856 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0712 AC: 10820 AN: 151974 Hom.: 620 Cov.: 32 AF XY: 0.0691 AC XY: 5136 AN XY: 74296

African (AFR) AF: 0.166 AC: 6869 AN: 41448

American (AMR) AF: 0.0530 AC: 810 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4812

European-Finnish (FIN) AF: 0.0129 AC: 136 AN: 10572

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2520 AN: 67904

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0612 Hom.: 142

Bravo AF: 0.0795

Asia WGS AF: 0.0170 AC: 60 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.6
DANN	Benign	0.41
PhyloP100		-0.33
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: rs10130695; hg19: chr14-60755984;