chr4-88265027-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_152542.5(PPM1K):c.961G>A(p.Glu321Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0017 in 1,614,096 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0088 ( 21 hom., cov: 33)
Exomes 𝑓: 0.00096 ( 20 hom. )
Consequence
PPM1K
NM_152542.5 missense
NM_152542.5 missense
Scores
1
5
9
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
PPM1K (HGNC:25415): (protein phosphatase, Mg2+/Mn2+ dependent 1K) This gene encodes a member of the PPM family of Mn2+/Mg2+-dependent protein phosphatases. The encoded protein, essential for cell survival and development, is targeted to the mitochondria where it plays a key role in regulation of the mitochondrial permeability transition pore. [provided by RefSeq, Sep 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00920701).
BP6
?
Variant 4-88265027-C-T is Benign according to our data. Variant chr4-88265027-C-T is described in ClinVar as [Benign]. Clinvar id is 775998.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00878 (1336/152216) while in subpopulation AFR AF= 0.0298 (1238/41528). AF 95% confidence interval is 0.0284. There are 21 homozygotes in gnomad4. There are 622 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPM1K | NM_152542.5 | c.961G>A | p.Glu321Lys | missense_variant | 6/7 | ENST00000608933.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPM1K | ENST00000608933.6 | c.961G>A | p.Glu321Lys | missense_variant | 6/7 | 1 | NM_152542.5 | P1 | |
PPM1K | ENST00000508256.5 | c.304G>A | p.Glu102Lys | missense_variant | 5/6 | 2 | |||
PPM1K | ENST00000295908.11 | c.853-2301G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00878 AC: 1335AN: 152098Hom.: 21 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00238 AC: 598AN: 251408Hom.: 12 AF XY: 0.00154 AC XY: 209AN XY: 135884
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GnomAD4 exome AF: 0.000960 AC: 1403AN: 1461880Hom.: 20 Cov.: 31 AF XY: 0.000807 AC XY: 587AN XY: 727242
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ESP6500AA
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137
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344
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maple syrup urine disease, mild variant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at