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GeneBe

17-58756169-G-T

Variant summary

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

The NM_014906.5(PPM1E):c.172G>T(p.Ala58Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PPM1E
NM_014906.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67
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=0.109622926).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPM1ENM_014906.5 linkuse as main transcriptc.172G>T p.Ala58Ser missense_variant 1/7 ENST00000308249.4
PPM1ENR_048561.1 linkuse as main transcriptn.301G>T non_coding_transcript_exon_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPM1EENST00000308249.4 linkuse as main transcriptc.172G>T p.Ala58Ser missense_variant 1/71 NM_014906.5 P1Q8WY54-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 30, 2023The c.172G>T (p.A58S) alteration is located in exon 1 (coding exon 1) of the PPM1E gene. This alteration results from a G to T substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.063
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.46
T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.060
N
REVEL
Benign
0.080
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.57
T
Vest4
0.20
MutPred
0.26
Gain of phosphorylation at A58 (P = 0.0013);
MVP
0.043
MPC
0.96
ClinPred
0.58
D
GERP RS
4.2
Varity_R
0.26
gMVP
0.10

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: chr17-56833530; API