3-52248184-C-T

Variant summary

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

The NM_144641.4(PPM1M):​c.742C>T​(p.Pro248Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

PPM1M
NM_144641.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55
Variant links:
Genes affected
PPM1M (HGNC:26506): (protein phosphatase, Mg2+/Mn2+ dependent 1M) Predicted to enable manganese ion binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.1561296).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPM1MNM_144641.4 linkuse as main transcriptc.742C>T p.Pro248Ser missense_variant 5/10 ENST00000323588.9 NP_653242.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPM1MENST00000323588.9 linkuse as main transcriptc.742C>T p.Pro248Ser missense_variant 5/101 NM_144641.4 ENSP00000319894 P1Q96MI6-5

Frequencies

GnomAD3 genomes
AF:
0.000375
AC:
57
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00130
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.0000801
AC:
20
AN:
249658
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134936
show subpopulations
Gnomad AFR exome
AF:
0.00106
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000240
AC:
35
AN:
1461056
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
726706
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.0000896
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:
0.0000331
GnomAD4 genome
AF:
0.000375
AC:
57
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.000283
AC XY:
21
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00130
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000956
Alfa
AF:
0.0000555
Hom.:
0
Bravo
AF:
0.000378
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11

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 GeneticsAug 30, 2022The c.742C>T (p.P248S) alteration is located in exon 5 (coding exon 5) of the PPM1M gene. This alteration results from a C to T substitution at nucleotide position 742, causing the proline (P) at amino acid position 248 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
0.13
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T;T;.
Eigen
Benign
0.028
Eigen_PC
Benign
0.032
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.70
T;T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
.;M;.
MutationTaster
Benign
0.55
N;N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-4.6
.;D;D
REVEL
Benign
0.10
Sift
Uncertain
0.0030
.;D;D
Sift4G
Benign
0.067
T;T;T
Polyphen
0.19
B;B;.
Vest4
0.53
MVP
0.43
MPC
0.32
ClinPred
0.11
T
GERP RS
3.2
Varity_R
0.32
gMVP
0.52

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: rs138142007; hg19: chr3-52282200; API