chr6-83169251-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015599.3(PGM3):c.1612C>A(p.Pro538Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,614,020 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P538P) has been classified as Likely benign.
Frequency
Consequence
NM_015599.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM3 | NM_015599.3 | c.1612C>A | p.Pro538Thr | missense_variant | 13/13 | ENST00000513973.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM3 | ENST00000513973.6 | c.1612C>A | p.Pro538Thr | missense_variant | 13/13 | 1 | NM_015599.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000474 AC: 119AN: 251168Hom.: 1 AF XY: 0.000486 AC XY: 66AN XY: 135744
GnomAD4 exome AF: 0.000365 AC: 534AN: 1461730Hom.: 1 Cov.: 31 AF XY: 0.000338 AC XY: 246AN XY: 727176
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74468
ClinVar
Submissions by phenotype
Immunodeficiency 23 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | Apr 05, 2022 | This sequence change in PGM3 is predicted to replace proline with threonine at codon 538, p.(Pro538Thr). The proline residue is evolutionarily conserved (100 vertebrates, UCSC), and is not located in a known functional domain. There is a small physicochemical difference between proline and threonine. The highest population minor allele frequency in gnomAD v2.1 is 0.09% (110/128,980 alleles, 1 homozygote) in the European (non-Finnish) population. This variant has been reported as a variant of uncertain significance (ClinVar ID: 252565), and to our knowledge has not been reported in the literature in any individuals with immunodeficiency. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (5/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PP3. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 566 of the PGM3 protein (p.Pro566Thr). This variant is present in population databases (rs143654268, gnomAD 0.08%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with PGM3-related conditions. ClinVar contains an entry for this variant (Variation ID: 252565). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Nov 20, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at