chr7-56081712-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006213.5(PHKG1):c.836C>T(p.Ala279Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000967 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
PHKG1
NM_006213.5 missense
NM_006213.5 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 5.00
Genes affected
PHKG1 (HGNC:8930): (phosphorylase kinase catalytic subunit gamma 1) This gene is a member of the Ser/Thr protein kinase family and encodes a protein with one protein kinase domain and two calmodulin-binding domains. This protein is the catalytic member of a 16 subunit protein kinase complex which contains equimolar ratios of 4 subunit types. The complex is a crucial glycogenolytic regulatory enzyme. This gene has two pseudogenes at chromosome 7q11.21 and one at chromosome 11p11.12. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25035337).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKG1 | NM_006213.5 | c.836C>T | p.Ala279Val | missense_variant | 9/10 | ENST00000297373.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKG1 | ENST00000297373.7 | c.836C>T | p.Ala279Val | missense_variant | 9/10 | 1 | NM_006213.5 | P1 | |
PHKG1 | ENST00000452681.6 | c.932C>T | p.Ala311Val | missense_variant | 10/11 | 2 | |||
PHKG1 | ENST00000446428.5 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152114Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
12
AN:
152114
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 250988Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135768
GnomAD3 exomes
AF:
AC:
19
AN:
250988
Hom.:
AF XY:
AC XY:
11
AN XY:
135768
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461634Hom.: 0 Cov.: 35 AF XY: 0.0000880 AC XY: 64AN XY: 727132
GnomAD4 exome
AF:
AC:
144
AN:
1461634
Hom.:
Cov.:
35
AF XY:
AC XY:
64
AN XY:
727132
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74284
GnomAD4 genome
AF:
AC:
12
AN:
152114
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
74284
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
12
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2022 | The c.836C>T (p.A279V) alteration is located in exon 9 (coding exon 8) of the PHKG1 gene. This alteration results from a C to T substitution at nucleotide position 836, causing the alanine (A) at amino acid position 279 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
0.64
.;.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at