chr4-88265014-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152542.5(PPM1K):c.974C>T(p.Ala325Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A325T) has been classified as Uncertain significance.
Frequency
Consequence
NM_152542.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPM1K | NM_152542.5 | c.974C>T | p.Ala325Val | missense_variant | 6/7 | ENST00000608933.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPM1K | ENST00000608933.6 | c.974C>T | p.Ala325Val | missense_variant | 6/7 | 1 | NM_152542.5 | P1 | |
PPM1K | ENST00000508256.5 | c.317C>T | p.Ala106Val | missense_variant | 5/6 | 2 | |||
PPM1K | ENST00000295908.11 | c.853-2288C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152116Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251352Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135860
GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47AN XY: 727218
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152116Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74292
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2021 | The c.974C>T (p.A325V) alteration is located in exon 6 (coding exon 5) of the PPM1K gene. This alteration results from a C to T substitution at nucleotide position 974, causing the alanine (A) at amino acid position 325 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Maple syrup urine disease, mild variant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 325 of the PPM1K protein (p.Ala325Val). This variant is present in population databases (rs142490765, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PPM1K-related conditions. ClinVar contains an entry for this variant (Variation ID: 1000474). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at