chr14-60273608-T-G

Variant names:

• chr14-60273608-T-G
• rs1887104
• NM_021003.5:c.-20-9076T>G

Variant summary

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

The NM_021003.5(PPM1A):​c.-20-9076T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,936 control chromosomes in the GnomAD database, including 5,797 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 0.27 (5797 hom., cov: 31)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1A	NM_021003.5	c.-20-9076T>G		intron_variant	Intron 1 of 5	ENST00000395076.9	NP_066283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1A	ENST00000395076.9	c.-20-9076T>G		intron_variant	Intron 1 of 5	1	NM_021003.5	ENSP00000378514.4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40610 AN: 151816 Hom.: 5800 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.267 AC: 40627 AN: 151936 Hom.: 5797 Cov.: 31 AF XY: 0.264 AC XY: 19621 AN XY: 74280

African (AFR) AF: 0.361 AC: 14962 AN: 41406

American (AMR) AF: 0.206 AC: 3140 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1131 AN: 3462

East Asian (EAS) AF: 0.120 AC: 618 AN: 5170

South Asian (SAS) AF: 0.360 AC: 1734 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2059 AN: 10570

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16278 AN: 67948

Other (OTH) AF: 0.254 AC: 534 AN: 2100

Alfa AF: 0.249 Hom.: 4310

Bravo AF: 0.268

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		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: rs1887104; hg19: chr14-60740326;