17-60600593-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003620.4(PPM1D):c.179G>A(p.Gly60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,557,326 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 Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPM1D | NM_003620.4 | c.179G>A | p.Gly60Asp | missense_variant | 1/6 | ENST00000305921.8 | |
PPM1D | XR_007065507.1 | n.401G>A | non_coding_transcript_exon_variant | 1/7 | |||
PPM1D | XR_934577.3 | n.401G>A | non_coding_transcript_exon_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPM1D | ENST00000305921.8 | c.179G>A | p.Gly60Asp | missense_variant | 1/6 | 1 | NM_003620.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000261 AC: 4AN: 153502Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 83904
GnomAD4 exome AF: 0.0000107 AC: 15AN: 1405146Hom.: 0 Cov.: 31 AF XY: 0.00000576 AC XY: 4AN XY: 694000
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74340
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.179G>A (p.G60D) alteration is located in exon 1 (coding exon 1) of the PPM1D gene. This alteration results from a G to A substitution at nucleotide position 179, causing the glycine (G) at amino acid position 60 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 60 of the PPM1D protein (p.Gly60Asp). This variant is present in population databases (rs774135477, gnomAD 0.01%). 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: 2146371). 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