rs141733590

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 8P and 12B. PVS1BP6_Very_StrongBS2

The NM_000293.3(PHKB):c.39G>A(p.Trp13*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0016 in 1,613,112 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 22 hom. )

Consequence

PHKB
NM_000293.3 stop_gained

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.03

Publications

4 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 links:

ITFG1 (HGNC:30697): (integrin alpha FG-GAP repeat containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ITFG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 76 pathogenic variants in the truncated region.

BP6

Variant 16-47461389-G-A is Benign according to our data. Variant chr16-47461389-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 530957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PHKB	NM_000293.3	MANE Select	c.39G>A	p.Trp13*	stop_gained	Exon 1 of 31	NP_000284.1
PHKB	NM_001363837.1		c.39G>A	p.Trp13*	stop_gained	Exon 1 of 31	NP_001350766.1
PHKB	NM_001031835.3		c.-95G>A		5_prime_UTR	Exon 1 of 32	NP_001027005.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PHKB	ENST00000323584.10	TSL:1 MANE Select	c.39G>A	p.Trp13*	stop_gained	Exon 1 of 31	ENSP00000313504.5
PHKB	ENST00000567402.5	TSL:1	n.54G>A		non_coding_transcript_exon	Exon 1 of 11
PHKB	ENST00000566044.5	TSL:1	c.-95G>A		5_prime_UTR	Exon 1 of 32	ENSP00000456729.1

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

319

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00224

AC:

544

AN:

243322

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.00155

AC:

2259

AN:

1460828

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1183

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33458

American (AMR)

AF:

0.0000447

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.0146

AC:

774

AN:

52892

Middle Eastern (MID)

AF:

0.000709

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00124

AC:

1379

AN:

1111798

Other (OTH)

AF:

0.00111

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

124

248

372

496

620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00209

AC:

319

AN:

152284

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41578

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0137

AC:

145

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00232

AC:

158

AN:

67992

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

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:

0.00234

Hom.:

Bravo

AF:

0.000805

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00229

AC:

278

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease IXb (2)

not provided (1)

not specified (1)

PHKB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Uncertain

0.88

PhyloP100

6.0

Vest4

0.17

GERP RS

4.7

PromoterAI

-0.031

Neutral

(source)

Mutation Taster

=264/36

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over