17-58756362-C-T

Variant summary

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

The NM_014906.5(PPM1E):​c.365C>T​(p.Pro122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,376,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P122Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

PPM1E
NM_014906.5 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32
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=0.23609492).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPM1ENM_014906.5 linkc.365C>T p.Pro122Leu missense_variant Exon 1 of 7 ENST00000308249.4 NP_055721.3 Q8WY54-2
PPM1ENR_048561.1 linkn.494C>T non_coding_transcript_exon_variant Exon 1 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPM1EENST00000308249.4 linkc.365C>T p.Pro122Leu missense_variant Exon 1 of 7 1 NM_014906.5 ENSP00000312411.2 Q8WY54-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151936
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000245
AC:
3
AN:
1224880
Hom.:
0
Cov.:
33
AF XY:
0.00000335
AC XY:
2
AN XY:
596936
show subpopulations
Gnomad4 AFR exome
AF:
0.0000421
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000204
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000100
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151936
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74204
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0041
T
Eigen
Benign
0.12
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.38
T
M_CAP
Pathogenic
0.44
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.082
Sift
Benign
0.48
T
Sift4G
Benign
0.20
T
Vest4
0.42
MutPred
0.22
Loss of glycosylation at P122 (P = 0.004);
MVP
0.21
MPC
1.1
ClinPred
0.15
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.078
gMVP
0.18

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

LitVar

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

Other links and lift over

dbSNP: rs936724323; hg19: chr17-56833723; API