rs16945474
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000293.3(PHKB):āc.2309A>Gā(p.Tyr770Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,611,382 control chromosomes in the GnomAD database, including 2,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.069 ( 610 hom., cov: 32)
Exomes š: 0.041 ( 1580 hom. )
Consequence
PHKB
NM_000293.3 missense
NM_000293.3 missense
Scores
3
6
6
Clinical Significance
Conservation
PhyloP100: 8.19
Genes affected
PHKB (HGNC:8927): (phosphorylase kinase regulatory subunit beta) 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, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, 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 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0038224757).
BP6
?
Variant 16-47663707-A-G is Benign according to our data. Variant chr16-47663707-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-47663707-A-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKB | NM_000293.3 | c.2309A>G | p.Tyr770Cys | missense_variant | 24/31 | ENST00000323584.10 | |
PHKB | NM_001363837.1 | c.2309A>G | p.Tyr770Cys | missense_variant | 24/31 | ||
PHKB | NM_001031835.3 | c.2288A>G | p.Tyr763Cys | missense_variant | 25/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKB | ENST00000323584.10 | c.2309A>G | p.Tyr770Cys | missense_variant | 24/31 | 1 | NM_000293.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0695 AC: 10578AN: 152174Hom.: 611 Cov.: 32
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GnomAD3 exomes AF: 0.0404 AC: 10154AN: 251204Hom.: 307 AF XY: 0.0393 AC XY: 5338AN XY: 135774
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GnomAD4 exome AF: 0.0411 AC: 60021AN: 1459090Hom.: 1580 Cov.: 29 AF XY: 0.0405 AC XY: 29427AN XY: 726024
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GnomAD4 genome ? AF: 0.0695 AC: 10583AN: 152292Hom.: 610 Cov.: 32 AF XY: 0.0674 AC XY: 5019AN XY: 74470
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144
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178
ESP6500AA
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671
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 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 | - | - - |
Glycogen storage disease IXb Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 13, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;.
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;T
Polyphen
P;.;B;.
Vest4
MPC
0.56
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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