rs9934849

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000323584.10(PHKB):ā€‹c.2459A>Gā€‹(p.Glu820Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E820V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

PHKB
ENST00000323584.10 missense

Scores

11
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.22
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36591).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PHKBNM_000293.3 linkuse as main transcriptc.2459A>G p.Glu820Gly missense_variant 26/31 ENST00000323584.10 NP_000284.1
PHKBNM_001363837.1 linkuse as main transcriptc.2459A>G p.Glu820Gly missense_variant 26/31 NP_001350766.1
PHKBNM_001031835.3 linkuse as main transcriptc.2438A>G p.Glu813Gly missense_variant 27/32 NP_001027005.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PHKBENST00000323584.10 linkuse as main transcriptc.2459A>G p.Glu820Gly missense_variant 26/311 NM_000293.3 ENSP00000313504 Q93100-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251246
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461804
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.061
T
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
.;.;T;D
Eigen
Benign
0.088
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.37
T;T;T;T
MetaSVM
Uncertain
-0.073
T
MutationAssessor
Benign
1.8
.;L;L;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.4
N;N;N;.
REVEL
Uncertain
0.48
Sift
Uncertain
0.010
D;D;D;.
Sift4G
Benign
0.39
T;T;T;D
Polyphen
0.38
B;.;B;.
Vest4
0.45
MutPred
0.40
.;Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);.;
MVP
0.89
MPC
0.25
ClinPred
0.64
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9934849; hg19: chr16-47703157; API