3-52247065-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144641.4(PPM1M):​c.434G>A​(p.Arg145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,565,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PPM1M
NM_144641.4 missense

Scores

1
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32646447).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPM1MNM_144641.4 linkuse as main transcriptc.434G>A p.Arg145His missense_variant 3/10 ENST00000323588.9 NP_653242.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPM1MENST00000323588.9 linkuse as main transcriptc.434G>A p.Arg145His missense_variant 3/101 NM_144641.4 ENSP00000319894 P1Q96MI6-5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.0000114
AC:
2
AN:
176202
Hom.:
0
AF XY:
0.0000213
AC XY:
2
AN XY:
93926
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000414
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000138
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000106
AC:
15
AN:
1412976
Hom.:
0
Cov.:
32
AF XY:
0.0000158
AC XY:
11
AN XY:
698342
show subpopulations
Gnomad4 AFR exome
AF:
0.0000620
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000124
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000837
AC:
1

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 02, 2022The c.434G>A (p.R145H) alteration is located in exon 3 (coding exon 3) of the PPM1M gene. This alteration results from a G to A substitution at nucleotide position 434, causing the arginine (R) at amino acid position 145 to be replaced by a histidine (H). 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
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.0081
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.56
D;D;D;D
PrimateAI
Uncertain
0.57
T
Sift4G
Benign
0.54
T
Polyphen
1.0
D
Vest4
0.39
MutPred
0.54
Loss of solvent accessibility (P = 0.1077);
MVP
0.40
ClinPred
0.38
T
GERP RS
4.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs770380330; hg19: chr3-52281081; COSMIC: COSV56599997; COSMIC: COSV56599997; API