14-60283647-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.927
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPM1ANM_021003.5 linkuse as main transcriptc.834+110C>T intron_variant ENST00000395076.9 NP_066283.1 P35813-1A0A024R6A5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPM1AENST00000395076.9 linkuse as main transcriptc.834+110C>T intron_variant 1 NM_021003.5 ENSP00000378514.4 P35813-1

Frequencies

GnomAD3 genomes
AF:
0.374
AC:
56797
AN:
151900
Hom.:
11832
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.588
Gnomad4 AMR exome
AF:
0.256
Gnomad4 ASJ exome
AF:
0.443
Gnomad4 EAS exome
AF:
0.125
Gnomad4 SAS exome
AF:
0.458
Gnomad4 FIN exome
AF:
0.263
Gnomad4 NFE exome
AF:
0.334
Gnomad4 OTH exome
AF:
0.348
GnomAD4 genome
AF:
0.374
AC:
56855
AN:
152020
Hom.:
11849
Cov.:
32
AF XY:
0.368
AC XY:
27337
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.565
Gnomad4 AMR
AF:
0.279
Gnomad4 ASJ
AF:
0.429
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.448
Gnomad4 FIN
AF:
0.263
Gnomad4 NFE
AF:
0.309
Gnomad4 OTH
AF:
0.353
Alfa
AF:
0.317
Hom.:
13366
Bravo
AF:
0.381
Asia WGS
AF:
0.297
AC:
1033
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
2.6
DANN
Benign
0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8012816; hg19: chr14-60750365; API