17-60600542-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_003620.4(PPM1D):c.128G>A(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,554,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003620.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPM1D | NM_003620.4 | c.128G>A | p.Arg43Gln | missense_variant | Exon 1 of 6 | ENST00000305921.8 | NP_003611.1 | |
PPM1D | XR_007065507.1 | n.350G>A | non_coding_transcript_exon_variant | Exon 1 of 7 | ||||
PPM1D | XR_934577.3 | n.350G>A | non_coding_transcript_exon_variant | Exon 1 of 7 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000132 AC: 20AN: 150964Hom.: 0 AF XY: 0.000123 AC XY: 10AN XY: 81262
GnomAD4 exome AF: 0.000133 AC: 187AN: 1402114Hom.: 0 Cov.: 31 AF XY: 0.000133 AC XY: 92AN XY: 692020
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 23, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 43 of the PPM1D protein (p.Arg43Gln). This variant is present in population databases (rs568868564, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PPM1D-related conditions. ClinVar contains an entry for this variant (Variation ID: 2188484). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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