Genetic Variant PHKA1:c.*1263_*1264dupGT (chrX-72579737-T-TAC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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: 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 link	c.1263_1264dupGT		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.1263_1264dupGT	3_prime_UTR_variant	Exon 32 of 32	1	NM_002637.4	ENSP00000362643.4	P46020-1
PHKA1	ENST00000339490.7 link	c.1263_1264dupGT	3_prime_UTR_variant	Exon 31 of 31	1		ENSP00000342469.3	P46020-2
PHKA1	ENST00000541944.5 link	c.1263_1264dupGT	3_prime_UTR_variant	Exon 30 of 30	1		ENSP00000441251.1	P46020-3
PHKA1	ENST00000373545.7 link	c.1263_1264dupGT	3_prime_UTR_variant	Exon 32 of 32	5		ENSP00000362646.3	A6NIT2

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

8222

AN:

106146

Hom.:

802

Cov.:

show subpopulations

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:

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:

0.0776

AC:

8236

AN:

106163

Hom.:

801

Cov.:

AF XY:

0.0603

AC XY:

1815

AN XY:

30101

show subpopulations

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:

AN:

2534

East Asian (EAS)

AF:

0.00664

AC:

AN:

3462

South Asian (SAS)

AF:

0.0135

AC:

AN:

2450

European-Finnish (FIN)

AF:

0.000951

AC:

AN:

5259

Middle Eastern (MID)

AF:

0.0423

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00406

AC:

208

AN:

51268

Other (OTH)

AF:

0.0612

AC:

AN:

1439

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

234

467

701

934

1168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000349

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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)

(source)

Splicing

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

Publications

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X-72579737-T-TAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over