chrX-72623285-AGAG-A

Variant names:

• chrX-72623285-AGAG-A
• rs886038517
• NM_002637.4:c.1794-13_1794-11delCTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_002637.4(PHKA1):​c.1794-13_1794-11delCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: PHKA1 NM_002637.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.910
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-72623285-AGAG-A is Benign according to our data. Variant chrX-72623285-AGAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 258783.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002637.4. 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
	PHKA1	NM_002637.4	MANE Select	c.1794-13_1794-11delCTC		intron	N/A	NP_002628.2	P46020-1
	PHKA1	NM_001431068.1		c.1794-13_1794-11delCTC		intron	N/A	NP_001417997.1	A6NMN0
	PHKA1	NM_001122670.2		c.1794-13_1794-11delCTC		intron	N/A	NP_001116142.1	P46020-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKA1	ENST00000373542.9	TSL:1 MANE Select	c.1794-13_1794-11delCTC		intron	N/A	ENSP00000362643.4	P46020-1
	PHKA1	ENST00000339490.7	TSL:1	c.1794-13_1794-11delCTC		intron	N/A	ENSP00000342469.3	P46020-2
	PHKA1	ENST00000541944.5	TSL:1	c.1794-13_1794-11delCTC		intron	N/A	ENSP00000441251.1	P46020-3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.26e-7 AC: 1 AN: 1080086 Hom.: 0 AF XY: 0.00000289 AC XY: 1 AN XY: 346166

African (AFR) AF: 0.00 AC: 0 AN: 26079

American (AMR) AF: 0.00 AC: 0 AN: 34843

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19236

East Asian (EAS) AF: 0.00 AC: 0 AN: 30021

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 826898

Other (OTH) AF: 0.00 AC: 0 AN: 45499

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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
PhyloP100		0.91

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: rs886038517; hg19: chrX-71843135;