Genetic Variant PRKX:p.Pro130Pro (chrX-3655358-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005044.5(PRKX):c.390G>A(p.Pro130Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,210,768 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 150 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00042 ( 0 hom. 144 hem. )

Consequence

PRKX
NM_005044.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.543

Publications

2 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-3655358-C-T is Benign according to our data. Variant chrX-3655358-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659892.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.543 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 6 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.390G>A	p.Pro130Pro	synonymous	Exon 3 of 9	NP_005035.1	P51817

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKX	ENST00000262848.6	TSL:1 MANE Select	c.390G>A	p.Pro130Pro	synonymous	Exon 3 of 9	ENSP00000262848.5	P51817
PRKX	ENST00000910398.1		c.390G>A	p.Pro130Pro	synonymous	Exon 3 of 9	ENSP00000580457.1
PRKX	ENST00000953311.1		c.390G>A	p.Pro130Pro	synonymous	Exon 3 of 9	ENSP00000623370.1

Frequencies

GnomAD3 genomes

AF:

0.000267

AC:

AN:

112484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

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:

0.000357

Gnomad OTH

AF:

0.000659

GnomAD2 exomes

AF:

0.000251

AC:

AN:

183020

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000419

AC:

460

AN:

1098231

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

144

AN XY:

363589

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000505

AC:

425

AN:

842130

Other (OTH)

AF:

0.000651

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000267

AC:

AN:

112537

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

34705

show subpopulations

African (AFR)

AF:

0.000225

AC:

AN:

31057

American (AMR)

AF:

0.000282

AC:

AN:

10631

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2733

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000357

AC:

AN:

53270

Other (OTH)

AF:

0.000651

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000434

Hom.:

Bravo

AF:

0.000272

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.52

(source)

DANN

Benign

0.89

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism

(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