rs149219369
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000292.3(PHKA2):āc.742A>Cā(p.Arg248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,172,943 control chromosomes in the GnomAD database, including 3 homozygotes. There are 602 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0013 ( 0 hom., 42 hem., cov: 23)
Exomes š: 0.0018 ( 3 hom. 560 hem. )
Consequence
PHKA2
NM_000292.3 synonymous
NM_000292.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.63
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant X-18941651-T-G is Benign according to our data. Variant chrX-18941651-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 198712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18941651-T-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.63 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0013 (147/113213) while in subpopulation NFE AF= 0.0023 (123/53430). AF 95% confidence interval is 0.00197. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 42 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKA2 | NM_000292.3 | c.742A>C | p.Arg248= | synonymous_variant | 8/33 | ENST00000379942.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKA2 | ENST00000379942.5 | c.742A>C | p.Arg248= | synonymous_variant | 8/33 | 1 | NM_000292.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00130 AC: 147AN: 113213Hom.: 0 Cov.: 23 AF XY: 0.00119 AC XY: 42AN XY: 35341
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GnomAD3 exomes AF: 0.00119 AC: 219AN: 183338Hom.: 1 AF XY: 0.00114 AC XY: 77AN XY: 67782
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GnomAD4 exome AF: 0.00184 AC: 1949AN: 1059730Hom.: 3 Cov.: 25 AF XY: 0.00170 AC XY: 560AN XY: 330144
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GnomAD4 genome ? AF: 0.00130 AC: 147AN: 113213Hom.: 0 Cov.: 23 AF XY: 0.00119 AC XY: 42AN XY: 35341
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2018 | 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 | Eurofins Ntd Llc (ga) | Feb 23, 2015 | - - |
Glycogen storage disease IXa1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Computational scores
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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