NM_014634.4:c.315G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014634.4(PPM1F):​c.315G>T​(p.Glu105Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PPM1F
NM_014634.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34
Variant links:
Genes affected
PPM1F (HGNC:19388): (protein phosphatase, Mg2+/Mn2+ dependent 1F) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase can interact with Rho guanine nucleotide exchange factors (PIX), and thus block the effects of p21-activated kinase 1 (PAK), a protein kinase mediating biological effects downstream of Rho GTPases. Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G/CAMK-II) is found to be one of the substrates of this phosphatase. The overexpression of this phosphatase or CAMK2G has been shown to mediate caspase-dependent apoptosis. An alternatively spliced transcript variant has been identified, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]
PPM1F-AS1 (HGNC:40888): (PPM1F antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044789314).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPM1FNM_014634.4 linkc.315G>T p.Glu105Asp missense_variant Exon 3 of 8 ENST00000263212.10 NP_055449.1 P49593-1
PPM1FNM_001410836.1 linkc.-190G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 7 NP_001397765.1
PPM1FNM_001410836.1 linkc.-190G>T 5_prime_UTR_variant Exon 2 of 7 NP_001397765.1
PPM1F-AS1NR_147620.1 linkn.1336C>A non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPM1FENST00000263212.10 linkc.315G>T p.Glu105Asp missense_variant Exon 3 of 8 1 NM_014634.4 ENSP00000263212.5 P49593-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1425534
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
705570
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.15
DANN
Benign
0.73
DEOGEN2
Benign
0.034
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.41
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.045
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.21
N;N
REVEL
Benign
0.012
Sift
Benign
0.55
T;T
Sift4G
Benign
0.64
T;T
Polyphen
0.0010
B;B
Vest4
0.17
MutPred
0.16
Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP
0.29
MPC
0.36
ClinPred
0.056
T
GERP RS
-1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.026
gMVP
0.11

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: rs61736973; hg19: chr22-22293944; API