chr14-60268245-A-C

Variant names:

• chr14-60268245-A-C
• rs10142834
• NM_021003.5:c.-20-14439A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177952.3(PPM1A):​c.200-14439A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: PPM1A NM_177952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177952.3. 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.-20-14439A>C		intron	N/A	NP_066283.1
	PPM1A	NM_177952.3		c.200-14439A>C		intron	N/A	NP_808821.2
	PPM1A	NM_177951.3		c.-20-14439A>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.-20-14439A>C		intron	N/A	ENSP00000378514.4
	PPM1A	ENST00000325658.3	TSL:1	c.-20-14439A>C		intron	N/A	ENSP00000314850.3
	PPM1A	ENST00000531143.6	TSL:1	n.200-8760A>C		intron	N/A	ENSP00000437200.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 5831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.17

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: rs10142834; hg19: chr14-60734963;