X-72580371-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002637.4(PHKA1):c.*629_*630del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 112,512 control chromosomes in the GnomAD database, including 395 homozygotes. There are 2,810 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (392 hom., 2802 hem., cov: 20)
  • Exomes 𝑓: 0.067 (3 hom. 8 hem.)
• Consequence: PHKA1 NM_002637.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.754

Genes affected

PHKA1 (HGNC:8925): (phosphorylase kinase regulatory subunit alpha 1) 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, and the skeletal muscle isoform is encoded by this gene. 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, which are encoded by two different genes. 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 9D, also known as X-linked muscle glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. A pseudogene has been found on chromosome 1.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-72580371-CAG-C is Benign according to our data. Variant chrX-72580371-CAG-C is described in ClinVar as [Benign]. Clinvar id is 368638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHKA1	NM_002637.4	c.*629_*630del		3_prime_UTR_variant	32/32	ENST00000373542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHKA1	ENST00000373542.9	c.*629_*630del		3_prime_UTR_variant	32/32	1	NM_002637.4	P4
PHKA1	ENST00000339490.7	c.*629_*630del		3_prime_UTR_variant	31/31	1
PHKA1	ENST00000541944.5	c.*629_*630del		3_prime_UTR_variant	30/30	1
PHKA1	ENST00000373545.7	c.*629_*630del		3_prime_UTR_variant	32/32	5

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 9437 AN: 111836 Hom.: 393 Cov.: 20 AF XY: 0.0823 AC XY: 2801 AN XY: 34042

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0294

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0719

GnomAD4 exome AF: 0.0674 AC: 42 AN: 623 Hom.: 3 AF XY: 0.0650 AC XY: 8 AN XY: 123

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00980

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0843 AC: 9430 AN: 111889 Hom.: 392 Cov.: 20 AF XY: 0.0822 AC XY: 2802 AN XY: 34105

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0924 Hom.: 521

Bravo AF: 0.0772

Asia WGS AF: 0.214 AC: 537 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glycogen phosphorylase kinase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3070316; hg19: chrX-71800221;