Variant 7-56081712-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

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]

PHKG1 links:

SUMF2 (HGNC:):

SUMF2 links:

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 linkuse as main transcript	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 linkuse as main transcript	c.836C>T	p.Ala279Val	missense_variant	9/10	1	NM_006213.5	P1	Q16816-1
PHKG1	ENST00000452681.6 linkuse as main transcript	c.932C>T	p.Ala311Val	missense_variant	10/11	2			Q16816-2
PHKG1	ENST00000446428.5 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

250988

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461634

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000119

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000982

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.66

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.96

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.20

T;.;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.64

.;.;P

Vest4

0.40

MVP

0.90

MPC

0.17

ClinPred

0.21

GERP RS

3.4

Varity_R

0.073

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over