NM_014906.5:c.344C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014906.5(PPM1E):​c.344C>A​(p.Pro115Gln) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P115L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PPM1E
NM_014906.5 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.717
Variant links:
Genes affected
PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19857863).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPM1ENM_014906.5 linkc.344C>A p.Pro115Gln missense_variant Exon 1 of 7 ENST00000308249.4 NP_055721.3 Q8WY54-2
PPM1ENR_048561.1 linkn.473C>A non_coding_transcript_exon_variant Exon 1 of 6
LOC105371843XR_007065865.1 linkn.-236G>T upstream_gene_variant
LOC105371843XR_007065866.1 linkn.-231G>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPM1EENST00000308249.4 linkc.344C>A p.Pro115Gln missense_variant Exon 1 of 7 1 NM_014906.5 ENSP00000312411.2 Q8WY54-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1220244
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
594126
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.0058
T
Eigen
Benign
-0.063
Eigen_PC
Benign
-0.040
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.39
T
M_CAP
Pathogenic
0.31
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
0.53
N
REVEL
Benign
0.079
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.096
T
Vest4
0.29
MutPred
0.20
Loss of glycosylation at P115 (P = 0.0071);
MVP
0.043
MPC
0.97
ClinPred
0.66
D
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
Varity_R
0.093
gMVP
0.32

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56833702; API