Genetic Variant PRKX:c.952-9G>A (chrX-3612334-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005044.5(PRKX):c.952-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,204,527 control chromosomes in the GnomAD database, including 4 homozygotes. There are 999 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., 44 hem., cov: 22)

Exomes 𝑓: 0.0027 ( 4 hom. 955 hem. )

Consequence

PRKX
NM_005044.5 intron

Scores

Splicing: ADA: 0.00008753

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.64

Publications

0 publications found

Variant links:

Genes affected

PRKX (HGNC:9441): (protein kinase cAMP-dependent X-linked catalytic subunit) This gene encodes a serine threonine protein kinase that has similarity to the catalytic subunit of cyclic AMP dependent protein kinases. The encoded protein is developmentally regulated and may be involved in renal epithelial morphogenesis. This protein may also be involved in macrophage and granulocyte maturation. Abnormal recombination between this gene and a related pseudogene on chromosome Y is a frequent cause of sex reversal disorder in XX males and XY females. Pseudogenes of this gene are found on chromosomes X, 15 and Y. [provided by RefSeq, Feb 2010]

PRKX links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-3612334-C-T is Benign according to our data. Variant chrX-3612334-C-T is described in ClinVar as Benign. ClinVar VariationId is 784728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 44 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKX	NM_005044.5	MANE Select	c.952-9G>A		intron	N/A	NP_005035.1	P51817

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKX	ENST00000262848.6	TSL:1 MANE Select	c.952-9G>A	intron	N/A	ENSP00000262848.5	P51817
PRKX	ENST00000910398.1		c.952-9G>A	intron	N/A	ENSP00000580457.1
PRKX	ENST00000953311.1		c.952-9G>A	intron	N/A	ENSP00000623370.1

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

201

AN:

110888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00117

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000773

Gnomad FIN

AF:

0.000677

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00534

GnomAD2 exomes

AF:

0.00176

AC:

307

AN:

174571

AF XY:

0.00164

show subpopulations

Gnomad AFR exome

AF:

0.000545

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00268

AC:

2927

AN:

1093583

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

955

AN XY:

359263

show subpopulations

African (AFR)

AF:

0.000342

AC:

AN:

26292

American (AMR)

AF:

0.000894

AC:

AN:

34691

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19207

East Asian (EAS)

AF:

0.00

AC:

AN:

30028

South Asian (SAS)

AF:

0.00170

AC:

AN:

53062

European-Finnish (FIN)

AF:

0.000845

AC:

AN:

40258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.00314

AC:

2637

AN:

840011

Other (OTH)

AF:

0.00274

AC:

126

AN:

45932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

192

287

383

479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00181

AC:

201

AN:

110944

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33168

show subpopulations

African (AFR)

AF:

0.000360

AC:

AN:

30523

American (AMR)

AF:

0.00117

AC:

AN:

10293

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3532

South Asian (SAS)

AF:

0.000775

AC:

AN:

2581

European-Finnish (FIN)

AF:

0.000677

AC:

AN:

5911

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00309

AC:

164

AN:

53044

Other (OTH)

AF:

0.00527

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.00239

Hom.:

Bravo

AF:

0.00153

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.014

(source)

DANN

Benign

0.71

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.038

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over