chr3-52248659-T-G

Variant summary

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

The NM_144641.4(PPM1M):ā€‹c.937T>Gā€‹(p.Ser313Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000046 ( 0 hom. )

Consequence

PPM1M
NM_144641.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.823
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=0.10651809).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPM1MNM_144641.4 linkuse as main transcriptc.937T>G p.Ser313Ala missense_variant 7/10 ENST00000323588.9 NP_653242.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPM1MENST00000323588.9 linkuse as main transcriptc.937T>G p.Ser313Ala missense_variant 7/101 NM_144641.4 ENSP00000319894 P1Q96MI6-5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151906
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:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251200
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135758
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461698
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
727138
show subpopulations
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:
0.0000594
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151906
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74172
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:
0.0000589
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000165
AC:
2

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 19, 2023The c.937T>G (p.S313A) alteration is located in exon 7 (coding exon 7) of the PPM1M gene. This alteration results from a T to G substitution at nucleotide position 937, causing the serine (S) at amino acid position 313 to be replaced by an alanine (A). 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
0.060
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Benign
0.94
DEOGEN2
Benign
0.024
T;T;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.50
T;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.60
.;N;.
MutationTaster
Benign
0.98
N;N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.4
.;N;N
REVEL
Benign
0.020
Sift
Benign
0.19
.;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.19
MutPred
0.39
Gain of glycosylation at Y317 (P = 0.0121);.;.;
MVP
0.34
MPC
0.17
ClinPred
0.051
T
GERP RS
2.4
Varity_R
0.075
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs770755292; hg19: chr3-52282675; API