rs61733284
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000292.3(PHKA2):c.849T>A(p.Ile283Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,208,421 control chromosomes in the GnomAD database, including 45 homozygotes. There are 995 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 24 hom., 394 hem., cov: 23)
Exomes 𝑓: 0.0019 ( 21 hom. 601 hem. )
Consequence
PHKA2
NM_000292.3 synonymous
NM_000292.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.16
Genes affected
PHKA2 (HGNC:8926): (phosphorylase kinase regulatory subunit alpha 2) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9A, also known as X-linked liver glycogenosis. Alternatively spliced transcript variants have been reported, but the full-length nature of these variants has not been determined.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant X-18941544-A-T is Benign according to our data. Variant chrX-18941544-A-T is described in ClinVar as [Benign]. Clinvar id is 255779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.16 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1464/112491) while in subpopulation AFR AF= 0.042 (1302/30964). AF 95% confidence interval is 0.0402. There are 24 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 24 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PHKA2 | NM_000292.3 | c.849T>A | p.Ile283Ile | synonymous_variant | 8/33 | ENST00000379942.5 | NP_000283.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PHKA2 | ENST00000379942.5 | c.849T>A | p.Ile283Ile | synonymous_variant | 8/33 | 1 | NM_000292.3 | ENSP00000369274.4 |
Frequencies
GnomAD3 genomes AF: 0.0130 AC: 1462AN: 112437Hom.: 23 Cov.: 23 AF XY: 0.0114 AC XY: 394AN XY: 34591
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GnomAD3 exomes AF: 0.00428 AC: 786AN: 183449Hom.: 12 AF XY: 0.00271 AC XY: 184AN XY: 67887
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GnomAD4 exome AF: 0.00189 AC: 2073AN: 1095930Hom.: 21 Cov.: 29 AF XY: 0.00166 AC XY: 601AN XY: 361332
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GnomAD4 genome AF: 0.0130 AC: 1464AN: 112491Hom.: 24 Cov.: 23 AF XY: 0.0114 AC XY: 394AN XY: 34655
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Glycogen storage disease IXa1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 13, 2024 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at