3-52247064-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144641.4(PPM1M):c.433C>T(p.Arg145Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,563,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PPM1M
NM_144641.4 missense
NM_144641.4 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 2.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPM1M | NM_144641.4 | c.433C>T | p.Arg145Cys | missense_variant | 3/10 | ENST00000323588.9 | NP_653242.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPM1M | ENST00000323588.9 | c.433C>T | p.Arg145Cys | missense_variant | 3/10 | 1 | NM_144641.4 | ENSP00000319894 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000229 AC: 4AN: 174338Hom.: 0 AF XY: 0.0000108 AC XY: 1AN XY: 92848
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GnomAD4 exome AF: 0.0000149 AC: 21AN: 1411566Hom.: 0 Cov.: 32 AF XY: 0.0000115 AC XY: 8AN XY: 697486
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378
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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 submitter | clinical testing | Ambry Genetics | May 10, 2022 | The c.433C>T (p.R145C) alteration is located in exon 3 (coding exon 3) of the PPM1M gene. This alteration results from a C to T substitution at nucleotide position 433, causing the arginine (R) at amino acid position 145 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of solvent accessibility (P = 0.1077);
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at