Genetic Variant NM_000293.3:c.1363+13G>T (chr16-47596544-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.326

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, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

PHKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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	Effect	Exon Rank	Protein	UniProt
PHKB	NM_000293.3	MANE Select	c.1363+13G>T	intron	N/A	NP_000284.1	Q93100-1
PHKB	NM_001363837.1		c.1363+13G>T	intron	N/A	NP_001350766.1	Q93100-3
PHKB	NM_001031835.3		c.1342+13G>T	intron	N/A	NP_001027005.1	Q93100-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHKB	ENST00000323584.10	TSL:1 MANE Select	c.1363+13G>T	intron	N/A	ENSP00000313504.5	Q93100-1
PHKB	ENST00000566044.5	TSL:1	c.1342+13G>T	intron	N/A	ENSP00000456729.1	Q93100-4
PHKB	ENST00000940565.1		c.1441+13G>T	intron	N/A	ENSP00000610624.1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1889

AN:

152144

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0177

AC XY:

12868

AN XY:

725666

show subpopulations

African (AFR)

AF:

0.00222

AC:

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1135

2271

3406

4542

5677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.0124

AC:

1887

AN:

152262

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

942

AN XY:

74446

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0181

AC:

1228

AN:

68008

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

193

290

386

483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0167

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease IXb (2)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.8

(source)

DANN

Benign

0.75

PhyloP100

0.33

PromoterAI

-0.0069

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over