rs73749732
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_015599.3(PGM3):c.521G>T(p.Arg174Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,613,866 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R174R) has been classified as Likely benign.
Frequency
Consequence
NM_015599.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM3 | NM_015599.3 | c.521G>T | p.Arg174Leu | missense_variant | 5/13 | ENST00000513973.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM3 | ENST00000513973.6 | c.521G>T | p.Arg174Leu | missense_variant | 5/13 | 1 | NM_015599.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00241 AC: 366AN: 152168Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000676 AC: 170AN: 251426Hom.: 1 AF XY: 0.000493 AC XY: 67AN XY: 135892
GnomAD4 exome AF: 0.000297 AC: 434AN: 1461580Hom.: 5 Cov.: 30 AF XY: 0.000242 AC XY: 176AN XY: 727118
GnomAD4 genome ? AF: 0.00242 AC: 368AN: 152286Hom.: 2 Cov.: 32 AF XY: 0.00231 AC XY: 172AN XY: 74456
ClinVar
Submissions by phenotype
Immunodeficiency 23 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | PGM3 NM_001199917.1 exon 6 p.Arg202Leu (c.605G>T): This variant has not been reported in the literature but is present in 0.9% (220/24038) of African alleles, including 2 homozygotes, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs73749732). This variant is present in ClinVar (Variation ID:475003). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 24, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at