Genetic Variant PHKA1:c.*1259_*1264dupGTGTGT (chrX-72579737-T-TACACAC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_002637.4(PHKA1):c.*1259_*1264dupGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000038 ( 0 hom., 2 hem., cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

PHKA1
NM_002637.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

0 publications found

Variant links:

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)

PHKA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 XL,AR geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKA1	NM_002637.4 link	c.1259_1264dupGTGTGT		3_prime_UTR_variant	Exon 32 of 32	ENST00000373542.9	NP_002628.2	P46020-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHKA1	ENST00000373542.9 link	c.1259_1264dupGTGTGT	3_prime_UTR_variant	Exon 32 of 32	1	NM_002637.4	ENSP00000362643.4	P46020-1
PHKA1	ENST00000339490.7 link	c.1259_1264dupGTGTGT	3_prime_UTR_variant	Exon 31 of 31	1		ENSP00000342469.3	P46020-2
PHKA1	ENST00000541944.5 link	c.1259_1264dupGTGTGT	3_prime_UTR_variant	Exon 30 of 30	1		ENSP00000441251.1	P46020-3
PHKA1	ENST00000373545.7 link	c.1259_1264dupGTGTGT	3_prime_UTR_variant	Exon 32 of 32	5		ENSP00000362646.3	A6NIT2

Frequencies

GnomAD3 genomes

AF:

0.0000377

AC:

AN:

106228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0000377

AC:

AN:

106228

Hom.:

Cov.:

AF XY:

0.0000664

AC XY:

AN XY:

30122

show subpopulations

African (AFR)

AF:

0.000138

AC:

AN:

29043

American (AMR)

AF:

0.00

AC:

AN:

9844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2534

East Asian (EAS)

AF:

0.00

AC:

AN:

3476

South Asian (SAS)

AF:

0.00

AC:

AN:

2461

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5265

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51281

Other (OTH)

AF:

0.00

AC:

AN:

1425

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

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

Publications

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chrX-72579737-T-TACACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over