rs117536391

Variant names:

• chr16-47596544-G-T
• rs117536391
• NM_000293.3:c.1363+13G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000293.3(PHKB):​c.1363+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,610,608 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.017 (305 hom.)
• Consequence: PHKB NM_000293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.326
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 16-47596544-G-T is Benign according to our data. Variant chr16-47596544-G-T is described in ClinVar as Benign. ClinVar VariationId is 257171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0124 (1887/152262) while in subpopulation SAS AF = 0.0328 (158/4822). AF 95% confidence interval is 0.0286. There are 19 homozygotes in GnomAd4. There are 942 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKB	NM_000293.3	c.1363+13G>T		intron_variant	Intron 13 of 30	ENST00000323584.10	NP_000284.1
PHKB	NM_001363837.1	c.1363+13G>T		intron_variant	Intron 13 of 30		NP_001350766.1
PHKB	NM_001031835.3	c.1342+13G>T		intron_variant	Intron 14 of 31		NP_001027005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKB	ENST00000323584.10	c.1363+13G>T		intron_variant	Intron 13 of 30	1	NM_000293.3	ENSP00000313504.5

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1889 AN: 152144 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.0165 AC: 4153 AN: 250936 AF XY: 0.0185

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00627

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0203

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0168 AC: 24539 AN: 1458346 Hom.: 305 Cov.: 29 AF XY: 0.0177 AC XY: 12868 AN XY: 725666

African (AFR) AF: 0.00222 AC: 74 AN: 33348

American (AMR) AF: 0.00630 AC: 281 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 362 AN: 26088

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39658

South Asian (SAS) AF: 0.0378 AC: 3255 AN: 86064

European-Finnish (FIN) AF: 0.0188 AC: 1005 AN: 53414

Middle Eastern (MID) AF: 0.0255 AC: 147 AN: 5756

European-Non Finnish (NFE) AF: 0.0166 AC: 18461 AN: 1109162

Other (OTH) AF: 0.0158 AC: 952 AN: 60264

GnomAD4 genome AF: 0.0124 AC: 1887 AN: 152262 Hom.: 19 Cov.: 32 AF XY: 0.0127 AC XY: 942 AN XY: 74446

African (AFR) AF: 0.00248 AC: 103 AN: 41550

American (AMR) AF: 0.00758 AC: 116 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4822

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1228 AN: 68008

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.0167 Hom.: 7

Bravo AF: 0.0106

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 17, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jun 07, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		0.33
PromoterAI		-0.0069	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117536391; hg19: chr16-47630455;