rs56268318

Positions:

chr16-47587662-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000293.3(PHKB):c.775-6G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,607,860 control chromosomes in the GnomAD database, including 5,304 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2299 hom., cov: 32)

Exomes 𝑓: 0.045 ( 3005 hom. )

Consequence

PHKB
NM_000293.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000006794

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.61

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-47587662-G-C is Benign according to our data. Variant chr16-47587662-G-C is described in ClinVar as [Benign]. Clinvar id is 257179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-47587662-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PHKB	NM_000293.3 linkuse as main transcript	c.775-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000323584.10
PHKB	NM_001031835.3 linkuse as main transcript	c.754-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PHKB	NM_001363837.1 linkuse as main transcript	c.775-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHKB	ENST00000323584.10 linkuse as main transcript	c.775-6G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000293.3		Q93100-1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17776

AN:

151912

Hom.:

2278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0412

Gnomad OTH

AF:

0.0982

GnomAD3 exomes

AF:

0.0524

AC:

13140

AN:

250894

Hom.:

970

AF XY:

0.0477

AC XY:

6465

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0141

Gnomad SAS exome

AF:

0.0275

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0410

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0454

AC:

66063

AN:

1455830

Hom.:

3005

Cov.:

AF XY:

0.0440

AC XY:

31900

AN XY:

724696

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0306

Gnomad4 EAS exome

AF:

0.00772

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.0156

Gnomad4 NFE exome

AF:

0.0413

Gnomad4 OTH exome

AF:

0.0545

GnomAD4 genome

AF:

0.117

AC:

17840

AN:

152030

Hom.:

2299

Cov.:

AF XY:

0.114

AC XY:

8457

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.0621

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.0285

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0412

Gnomad4 OTH

AF:

0.0981

Alfa

AF:

0.0611

Hom.:

202

Bravo

AF:

0.129

Asia WGS

AF:

0.0390

AC:

137

AN:

3478

EpiCase

AF:

0.0480

EpiControl

AF:

0.0470

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 23, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease IXb

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 13, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.5

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000068

dbscSNV1_RF

Benign

0.0080

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over