rs532057230

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_000293.3(PHKB):c.2459_2461delAAG(p.Glu820del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,614,042 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 40 hom. )

Consequence

PHKB
NM_000293.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 9.26

Publications

1 publications found

Variant links:

Genes affected

PHKB (HGNC:8927): (phosphorylase kinase regulatory subunit beta) 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, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, 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 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.[provided by RefSeq, Feb 2010]

PHKB Gene-Disease associations (from GenCC):

glycogen storage disease IXb
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

PHKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000293.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 16-47669238-TGAA-T is Benign according to our data. Variant chr16-47669238-TGAA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0045 (686/152278) while in subpopulation NFE AF = 0.00272 (185/68014). AF 95% confidence interval is 0.0024. There are 5 homozygotes in GnomAd4. There are 445 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKB	NM_000293.3 link	c.2459_2461delAAG	p.Glu820del	disruptive_inframe_deletion	Exon 26 of 31	ENST00000323584.10	NP_000284.1	Q93100-1
PHKB	NM_001363837.1 link	c.2459_2461delAAG	p.Glu820del	disruptive_inframe_deletion	Exon 26 of 31		NP_001350766.1
PHKB	NM_001031835.3 link	c.2438_2440delAAG	p.Glu813del	disruptive_inframe_deletion	Exon 27 of 32		NP_001027005.1	Q93100-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKB	ENST00000323584.10 link	c.2459_2461delAAG	p.Glu820del	disruptive_inframe_deletion	Exon 26 of 31	1	NM_000293.3	ENSP00000313504.5		Q93100-1

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

686

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00496

AC:

1247

AN:

251212

AF XY:

0.00483

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.00290

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00301

AC:

4394

AN:

1461764

Hom.:

AF XY:

0.00294

AC XY:

2138

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33476

American (AMR)

AF:

0.00145

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0355

AC:

1899

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00205

AC:

2276

AN:

1111906

Other (OTH)

AF:

0.00233

AC:

141

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

217

434

651

868

1085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00450

AC:

686

AN:

152278

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

445

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41556

American (AMR)

AF:

0.00196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0421

AC:

447

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00272

AC:

185

AN:

68014

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.00158

EpiCase

AF:

0.00234

EpiControl

AF:

0.00172

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 31, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PHKB: BS1, BS2 -

Glycogen phosphorylase kinase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease IXb

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

9.3

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over