Variant X-72599841-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001431068.1(PHKA1):c.3098T>C(p.Ile1033Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 549,092 control chromosomes in the GnomAD database, including 8,874 homozygotes. There are 21,183 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1674 hom., 4368 hem., cov: 22)

Exomes 𝑓: 0.11 ( 7200 hom. 16815 hem. )

Consequence

PHKA1
NM_001431068.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

PHKA1 (HGNC:8925): (phosphorylase kinase regulatory subunit alpha 1) 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, and the skeletal muscle isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are 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 9D, also known as X-linked muscle glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. A pseudogene has been found on chromosome 1.[provided by RefSeq, Feb 2010]

PHKA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.3429835E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHKA1	NM_002637.4 link	c.3072+2150T>C		intron_variant		ENST00000373542.9	NP_002628.2	P46020-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHKA1	ENST00000373542.9 link	c.3072+2150T>C		intron_variant		1	NM_002637.4	ENSP00000362643.4		P46020-1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

14689

AN:

110438

Hom.:

1675

Cov.:

AF XY:

0.133

AC XY:

4366

AN XY:

32736

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.0327

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00921

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.165

AC:

24100

AN:

145859

Hom.:

4251

AF XY:

0.133

AC XY:

6004

AN XY:

45229

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.679

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0261

Gnomad NFE exome

AF:

0.00939

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.110

AC:

48276

AN:

438600

Hom.:

7200

Cov.:

AF XY:

0.106

AC XY:

16815

AN XY:

158758

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.0283

Gnomad4 EAS exome

AF:

0.688

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.00984

Gnomad4 OTH exome

AF:

0.0984

GnomAD4 genome

AF:

0.133

AC:

14696

AN:

110492

Hom.:

1674

Cov.:

AF XY:

0.133

AC XY:

4368

AN XY:

32800

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.0327

Gnomad4 EAS

AF:

0.672

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.00921

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0682

Hom.:

980

Bravo

AF:

0.169

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00935

AC:

ESP6500AA

AF:

0.287

AC:

407

ESP6500EA

AF:

0.00967

AC:

ExAC

AF:

0.146

AC:

16573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.8

DANN

Benign

0.24

DEOGEN2

Benign

0.0058

T;T

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0000093

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.073

Sift

Benign

0.57

T;T

Sift4G

Benign

0.63

T;T

Vest4

0.098

ClinPred

0.0057

GERP RS

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over