rs144211929
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_000293.3(PHKB):āc.491A>Gā(p.Tyr164Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,591,424 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 32)
Exomes š: 0.00012 ( 1 hom. )
Consequence
PHKB
NM_000293.3 missense
NM_000293.3 missense
Scores
1
9
6
Clinical Significance
Conservation
PhyloP100: 3.57
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 -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014536291).
BP6
?
Variant 16-47511750-A-G is Benign according to our data. Variant chr16-47511750-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 319335.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000118 (18/152278) while in subpopulation EAS AF= 0.00328 (17/5178). AF 95% confidence interval is 0.00209. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKB | NM_000293.3 | c.491A>G | p.Tyr164Cys | missense_variant | 5/31 | ENST00000323584.10 | |
PHKB | NM_001363837.1 | c.491A>G | p.Tyr164Cys | missense_variant | 5/31 | ||
PHKB | NM_001031835.3 | c.470A>G | p.Tyr157Cys | missense_variant | 6/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKB | ENST00000323584.10 | c.491A>G | p.Tyr164Cys | missense_variant | 5/31 | 1 | NM_000293.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000314 AC: 79AN: 251394Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135858
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GnomAD4 exome AF: 0.000123 AC: 177AN: 1439146Hom.: 1 Cov.: 26 AF XY: 0.000118 AC XY: 85AN XY: 717312
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease IXb Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
Sift
Uncertain
D;T;T;T
Sift4G
Uncertain
T;T;T;T
Polyphen
0.99, 0.97
.;D;.;D
Vest4
0.42, 0.39, 0.38
MVP
MPC
0.15
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