NM_021003.5:c.834+110C>T

Variant names:

• chr14-60283647-C-T
• rs8012816
• NM_021003.5:c.834+110C>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.834+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,080,948 control chromosomes in the GnomAD database, including 65,249 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 0.37 (11849 hom., cov: 32)
  • Exomes 𝑓: 0.34 (53400 hom.)
• Consequence: PPM1A NM_021003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 12 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 = 0.559 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1A	NM_021003.5	MANE Select	c.834+110C>T		intron	N/A	NP_066283.1	P35813-1
	PPM1A	NM_177952.3		c.1053+110C>T		intron	N/A	NP_808821.2	P35813-3
	PPM1A	NM_177951.3		c.834+110C>T		intron	N/A	NP_808820.1	P35813-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1A	ENST00000395076.9	TSL:1 MANE Select	c.834+110C>T		intron	N/A	ENSP00000378514.4	P35813-1
	PPM1A	ENST00000325658.3	TSL:1	c.834+110C>T		intron	N/A	ENSP00000314850.3	P35813-2
	PPM1A	ENST00000531143.6	TSL:1	n.*858+110C>T		intron	N/A	ENSP00000437200.2	E9PNE1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56797 AN: 151900 Hom.: 11832 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.338 AC: 313740 AN: 928928 Hom.: 53400 AF XY: 0.340 AC XY: 159690 AN XY: 469320

African (AFR) AF: 0.588 AC: 12759 AN: 21696

American (AMR) AF: 0.256 AC: 6042 AN: 23592

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 7562 AN: 17088

East Asian (EAS) AF: 0.125 AC: 4359 AN: 34750

South Asian (SAS) AF: 0.458 AC: 26153 AN: 57130

European-Finnish (FIN) AF: 0.263 AC: 8722 AN: 33204

Middle Eastern (MID) AF: 0.394 AC: 1400 AN: 3554

European-Non Finnish (NFE) AF: 0.334 AC: 232106 AN: 695896

Other (OTH) AF: 0.348 AC: 14637 AN: 42018

GnomAD4 genome AF: 0.374 AC: 56855 AN: 152020 Hom.: 11849 Cov.: 32 AF XY: 0.368 AC XY: 27337 AN XY: 74306

African (AFR) AF: 0.565 AC: 23412 AN: 41446

American (AMR) AF: 0.279 AC: 4270 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3468

East Asian (EAS) AF: 0.152 AC: 789 AN: 5184

South Asian (SAS) AF: 0.448 AC: 2156 AN: 4810

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10548

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20990 AN: 67956

Other (OTH) AF: 0.353 AC: 748 AN: 2116

Alfa AF: 0.336 Hom.: 24901

Bravo AF: 0.381

Asia WGS AF: 0.297 AC: 1033 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8012816; hg19: chr14-60750365;