rs201392846
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_015599.3(PGM3):c.389+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,599,130 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00064 ( 2 hom. )
Consequence
PGM3
NM_015599.3 splice_region, intron
NM_015599.3 splice_region, intron
Scores
2
Splicing: ADA: 0.0001010
2
Clinical Significance
Conservation
PhyloP100: 0.592
Genes affected
PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 6-83188611-C-T is Benign according to our data. Variant chr6-83188611-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 475002.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PGM3 | NM_015599.3 | c.389+3G>A | splice_region_variant, intron_variant | ENST00000513973.6 | NP_056414.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PGM3 | ENST00000513973.6 | c.389+3G>A | splice_region_variant, intron_variant | 1 | NM_015599.3 | ENSP00000424874.1 | ||||
| PGM3 | ENST00000283977.9 | c.146+3G>A | splice_region_variant, intron_variant | 5 | ENSP00000283977.5 |
Frequencies
GnomAD3 genomes 0.000566 AC: 86AN: 151934Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000372 AC: 93AN: 250146Hom.: 0 AF XY: 0.000385 AC XY: 52AN XY: 135218
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GnomAD4 exome AF: 0.000641 AC: 928AN: 1447078Hom.: 2 Cov.: 30 AF XY: 0.000636 AC XY: 458AN XY: 720490
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GnomAD4 genome 0.000566 AC: 86AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.000632 AC XY: 47AN XY: 74354
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Immunodeficiency 23 Uncertain:2
| Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 07, 2021 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This sequence change falls in intron 4 of the PGM3 gene. It does not directly change the encoded amino acid sequence of the PGM3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201392846, gnomAD 0.07%). 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: 475002). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 03, 2024 | - - |
not provided Benign:1
| Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at