chrX-72579737-T-TAC

Variant names:

• chrX-72579737-T-TAC
• rs111688568
• NM_002637.4:c.*1263_*1264dupGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002637.4(PHKA1):​c.*1263_*1264dupGT 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
• Publications: 0 publications found

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]

PHKA1 Gene-Disease associations (from GenCC):

• glycogen storage disease IXd

  Inheritance: XL, AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHKA1	NM_002637.4	c.*1263_*1264dupGT		3_prime_UTR_variant	Exon 32 of 32	ENST00000373542.9	NP_002628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKA1	ENST00000373542.9	c.*1263_*1264dupGT		3_prime_UTR_variant	Exon 32 of 32	1	NM_002637.4	ENSP00000362643.4
PHKA1	ENST00000339490.7	c.*1263_*1264dupGT		3_prime_UTR_variant	Exon 31 of 31	1		ENSP00000342469.3
PHKA1	ENST00000541944.5	c.*1263_*1264dupGT		3_prime_UTR_variant	Exon 30 of 30	1		ENSP00000441251.1
PHKA1	ENST00000373545.7	c.*1263_*1264dupGT		3_prime_UTR_variant	Exon 32 of 32	5		ENSP00000362646.3

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 8222 AN: 106146 Hom.: 802 Cov.: 19

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31

Other (OTH) AF: 0.00 AC: 0 AN: 3

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

African (AFR) AF: 0.259 AC: 7523 AN: 29036

American (AMR) AF: 0.0351 AC: 345 AN: 9835

Ashkenazi Jewish (ASJ) AF: 0.000789 AC: 2 AN: 2534

East Asian (EAS) AF: 0.00664 AC: 23 AN: 3462

South Asian (SAS) AF: 0.0135 AC: 33 AN: 2450

European-Finnish (FIN) AF: 0.000951 AC: 5 AN: 5259

Middle Eastern (MID) AF: 0.0423 AC: 9 AN: 213

European-Non Finnish (NFE) AF: 0.00406 AC: 208 AN: 51268

Other (OTH) AF: 0.0612 AC: 88 AN: 1439

Alfa AF: 0.000349 Hom.: 7

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glycogen phosphorylase kinase deficiency Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs111688568; hg19: chrX-71799587;