X-72579737-T-TAC

Variant summary

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

The NM_002637.4(PHKA1):c.*1264_*1265insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (801 hom., 1815 hem., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PHKA1 NM_002637.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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-72579737-T-TAC is Benign according to our data. Variant chrX-72579737-T-TAC is described in ClinVar as [Benign]. Clinvar id is 368633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHKA1	NM_002637.4	c.*1264_*1265insGT		3_prime_UTR_variant	32/32	ENST00000373542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHKA1	ENST00000373542.9	c.*1264_*1265insGT		3_prime_UTR_variant	32/32	1	NM_002637.4	P4
PHKA1	ENST00000339490.7	c.*1264_*1265insGT		3_prime_UTR_variant	31/31	1
PHKA1	ENST00000541944.5	c.*1264_*1265insGT		3_prime_UTR_variant	30/30	1
PHKA1	ENST00000373545.7	c.*1264_*1265insGT		3_prime_UTR_variant	32/32	5

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 8222 AN: 106146 Hom.: 802 Cov.: 19 AF XY: 0.0601 AC XY: 1808 AN XY: 30072

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.000789

Gnomad EAS AF: 0.00691

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.000951

Gnomad MID AF: 0.0388

Gnomad NFE AF: 0.00406

Gnomad OTH AF: 0.0618

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0776 AC: 8236 AN: 106163 Hom.: 801 Cov.: 19 AF XY: 0.0603 AC XY: 1815 AN XY: 30101

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.000789

Gnomad4 EAS AF: 0.00664

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.000951

Gnomad4 NFE AF: 0.00406

Gnomad4 OTH AF: 0.0612

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs111688568; hg19: chrX-71799587;