chrX-18893578-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000292.3(PHKA2):c.3615G>C(p.Pro1205Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,210,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P1205P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 3 hem. )

Consequence

PHKA2
NM_000292.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.25

Publications

1 publications found

Variant links:

Genes affected

PHKA2 (HGNC:8926): (phosphorylase kinase regulatory subunit alpha 2) 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 hepatic 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 9A, also known as X-linked liver glycogenosis. Alternatively spliced transcript variants have been reported, but the full-length nature of these variants has not been determined.[provided by RefSeq, Feb 2010]

PHKA2 links:

PHKA2-AS1 (HGNC:44110): (PHKA2 antisense RNA 1)

PHKA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-18893578-C-G is Benign according to our data. Variant chrX-18893578-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2860103.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000888 (10/112557) while in subpopulation AMR AF = 0.00075 (8/10661). AF 95% confidence interval is 0.000373. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 4 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKA2	NM_000292.3 link	c.3615G>C	p.Pro1205Pro	synonymous_variant	Exon 33 of 33	ENST00000379942.5	NP_000283.1	P46019

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKA2	ENST00000379942.5 link	c.3615G>C	p.Pro1205Pro	synonymous_variant	Exon 33 of 33	1	NM_000292.3	ENSP00000369274.4		P46019

Frequencies

GnomAD3 genomes

AF:

0.0000889

AC:

AN:

112505

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000751

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000661

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

183223

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1097449

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362813

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26390

American (AMR)

AF:

0.000256

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

54130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841422

Other (OTH)

AF:

0.000109

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000888

AC:

AN:

112557

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34707

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31046

American (AMR)

AF:

0.000750

AC:

AN:

10661

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2699

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53288

Other (OTH)

AF:

0.000653

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.000287

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycogen storage disease IXa1

Benign:1

Dec 12, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.083

(source)

DANN

Benign

0.59

PhyloP100

-3.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over