rs3830242

Positions:

• chr16-47650775-TATTA-T
• chr16-47650775-TATTA-TATTAATTA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000293.3(PHKB):​c.1881-52_1881-49del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,394,238 control chromosomes in the GnomAD database, including 133,750 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11734 hom., cov: 0)
  • Exomes 𝑓: 0.43 (122016 hom.)
• Consequence: PHKB NM_000293.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.435

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-47650775-TATTA-T is Benign according to our data. Variant chr16-47650775-TATTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 257173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHKB	NM_000293.3	c.1881-52_1881-49del		intron_variant		ENST00000323584.10
PHKB	NM_001031835.3	c.1860-52_1860-49del		intron_variant
PHKB	NM_001363837.1	c.1881-52_1881-49del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHKB	ENST00000323584.10	c.1881-52_1881-49del		intron_variant		1	NM_000293.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55930 AN: 151558 Hom.: 11736 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.434 AC: 539108 AN: 1242560 Hom.: 122016 AF XY: 0.436 AC XY: 274562 AN XY: 629888

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.369 AC: 55946 AN: 151678 Hom.: 11734 Cov.: 0 AF XY: 0.375 AC XY: 27789 AN XY: 74092

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.389

Alfa AF: 0.368 Hom.: 1353

Bravo AF: 0.372

Asia WGS AF: 0.575 AC: 1997 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3830242; hg19: chr16-47684686;