16-30748403-G-A

Variant names:

• chr16-30748403-G-A
• rs879382458
• ENST00000866453.1:c.-106G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000424889.7(PHKG2):​c.-106G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000242 in 206,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PHKG2 ENST00000424889.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93
• Publications: 0 publications found

Genes affected

PHKG2 (HGNC:8931): (phosphorylase kinase catalytic subunit gamma 2) 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, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. 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 9C, also known as autosomal liver glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

PHKG2 Gene-Disease associations (from GenCC):

• glycogen storage disease IXc

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• glycogen storage disease due to liver phosphorylase kinase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260899 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424889.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	NM_000294.3	MANE Select	c.-106G>A		upstream_gene	N/A	NP_000285.1	P15735-1
	PHKG2	NM_001172432.2		c.-106G>A		upstream_gene	N/A	NP_001165903.1	P15735-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	ENST00000866453.1		c.-106G>A		5_prime_UTR	Exon 1 of 9	ENSP00000536512.1
	PHKG2	ENST00000424889.7	TSL:2	c.-106G>A		5_prime_UTR	Exon 1 of 11	ENSP00000388571.3	P15735-2
	PHKG2	ENST00000565924.5	TSL:3	c.-34G>A		5_prime_UTR	Exon 1 of 8	ENSP00000455091.1	H3BP07

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 2 AN: 54028 Hom.: 0 Cov.: 0 AF XY: 0.0000356 AC XY: 1 AN XY: 28082

African (AFR) AF: 0.00 AC: 0 AN: 652

American (AMR) AF: 0.000659 AC: 2 AN: 3034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1492

East Asian (EAS) AF: 0.00 AC: 0 AN: 2592

South Asian (SAS) AF: 0.00 AC: 0 AN: 7660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 32892

Other (OTH) AF: 0.00 AC: 0 AN: 3042

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152358 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.000196 AC: 3 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Glycogen storage disease IXc (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		3.9
PromoterAI		-0.13	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs879382458; hg19: chr16-30759724;