rs534374752

Variant names:

• chr16-30748488-C-G
• rs534374752
• NM_000294.3:c.-21C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-30748488-C-G
• chr16-30748488-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000294.3(PHKG2):​c.-21C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 401,956 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PHKG2 NM_000294.3 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.00008914
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-30748488-C-G is Benign according to our data. Variant chr16-30748488-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 389747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000131 (20/152386) while in subpopulation AMR AF = 0.000522 (8/15312). AF 95% confidence interval is 0.00026. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000294.3. 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.-21C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_000285.1	P15735-1
	PHKG2	NM_000294.3	MANE Select	c.-21C>G		splice_region	Exon 1 of 10	NP_000285.1	P15735-1
	PHKG2	NM_000294.3	MANE Select	c.-21C>G		5_prime_UTR	Exon 1 of 10	NP_000285.1	P15735-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.-21C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000455607.1	P15735-1
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.-21C>G		splice_region	Exon 1 of 10	ENSP00000455607.1	P15735-1
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.-21C>G		5_prime_UTR	Exon 1 of 10	ENSP00000455607.1	P15735-1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152268 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

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: 0.000478

GnomAD4 exome AF: 0.0000160 AC: 4 AN: 249570 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130424

African (AFR) AF: 0.000351 AC: 2 AN: 5700

American (AMR) AF: 0.000111 AC: 1 AN: 9016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7878

East Asian (EAS) AF: 0.00 AC: 0 AN: 15880

South Asian (SAS) AF: 0.00 AC: 0 AN: 27490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 152202

Other (OTH) AF: 0.0000670 AC: 1 AN: 14920

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152386 Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8 AN XY: 74516

African (AFR) AF: 0.000264 AC: 11 AN: 41602

American (AMR) AF: 0.000522 AC: 8 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000166

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.1
DANN	Benign	0.62
PhyloP100		-0.020
PromoterAI		0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000089
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs534374752; hg19: chr16-30759809;