16-30751319-C-T

Variant names:

• chr16-30751319-C-T
• rs4889504
• ENST00000569762.1:n.286C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000569762.1(PHKG2):​n.286C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,601,210 control chromosomes in the GnomAD database, including 790,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71214 hom., cov: 30)
  • Exomes 𝑓: 1.0 (719716 hom.)
• Consequence: PHKG2 ENST00000569762.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0350
• Publications: 7 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: STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• glycogen storage disease due to liver phosphorylase kinase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260899 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-30751319-C-T is Benign according to our data. Variant chr16-30751319-C-T is described in ClinVar as Benign. ClinVar VariationId is 255782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000569762.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	NM_000294.3	MANE Select	c.271+38C>T		intron	N/A	NP_000285.1
	PHKG2	NM_001172432.2		c.271+38C>T		intron	N/A	NP_001165903.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	ENST00000569762.1	TSL:1	n.286C>T		non_coding_transcript_exon	Exon 2 of 2
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.271+38C>T		intron	N/A	ENSP00000455607.1
	ENSG00000260899	ENST00000483578.1	TSL:5	n.821C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.967 AC: 146973 AN: 152052 Hom.: 71182 Cov.: 30

Gnomad AFR AF: 0.882

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.979

GnomAD2 exomes AF: 0.991 AC: 242688 AN: 244778 AF XY: 0.994

Gnomad AFR exome AF: 0.884

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.996 AC: 1443963 AN: 1449040 Hom.: 719716 Cov.: 32 AF XY: 0.997 AC XY: 719367 AN XY: 721490

African (AFR) AF: 0.874 AC: 29180 AN: 33374

American (AMR) AF: 0.995 AC: 44447 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 26055 AN: 26098

East Asian (EAS) AF: 0.999 AC: 39630 AN: 39676

South Asian (SAS) AF: 1.00 AC: 86092 AN: 86116

European-Finnish (FIN) AF: 1.00 AC: 45207 AN: 45208

Middle Eastern (MID) AF: 0.998 AC: 5743 AN: 5756

European-Non Finnish (NFE) AF: 1.00 AC: 1107811 AN: 1107922

Other (OTH) AF: 0.993 AC: 59798 AN: 60206

GnomAD4 genome AF: 0.966 AC: 147058 AN: 152170 Hom.: 71214 Cov.: 30 AF XY: 0.967 AC XY: 71966 AN XY: 74398

African (AFR) AF: 0.881 AC: 36538 AN: 41472

American (AMR) AF: 0.993 AC: 15193 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4810 AN: 4812

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68000 AN: 68022

Other (OTH) AF: 0.980 AC: 2063 AN: 2106

Alfa AF: 0.988 Hom.: 90535

Bravo AF: 0.962

Asia WGS AF: 0.990 AC: 3442 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disease IXc (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.56
PhyloP100		-0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4889504; hg19: chr16-30762640;