dbSNP rs139150166: PRKX:p.Val321Met (chrX-3612316-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005044.5(PRKX):c.961G>A(p.Val321Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,206,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.000048 ( 0 hom. 13 hem. )

Consequence

PRKX
NM_005044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0788362).

BS2

High Hemizygotes in GnomAd4 at 8 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.961G>A	p.Val321Met	missense	Exon 8 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.961G>A	p.Val321Met	missense	Exon 8 of 9	ENSP00000262848.5	P51817
PRKX	ENST00000910398.1		c.961G>A	p.Val321Met	missense	Exon 8 of 9	ENSP00000580457.1
PRKX	ENST00000953311.1		c.961G>A	p.Val321Met	missense	Exon 8 of 9	ENSP00000623370.1

Frequencies

GnomAD3 genomes

AF:

0.000352

AC:

AN:

110646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000292

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:

0.000670

GnomAD2 exomes

AF:

0.000112

AC:

AN:

179117

AF XY:

0.0000157

show subpopulations

Gnomad AFR exome

AF:

0.00115

Gnomad AMR exome

AF:

0.0000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000497

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000484

AC:

AN:

1095711

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

361193

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

26316

American (AMR)

AF:

0.0000859

AC:

AN:

34915

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19304

East Asian (EAS)

AF:

0.00

AC:

AN:

30096

South Asian (SAS)

AF:

0.00

AC:

AN:

53554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40407

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4114

European-Non Finnish (NFE)

AF:

0.00000951

AC:

AN:

840997

Other (OTH)

AF:

0.000196

AC:

AN:

46008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000361

AC:

AN:

110701

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

32949

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

30448

American (AMR)

AF:

0.000292

AC:

AN:

10289

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3514

South Asian (SAS)

AF:

0.00

AC:

AN:

2579

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5849

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52973

Other (OTH)

AF:

0.000661

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000841

Hom.:

Bravo

AF:

0.000461

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.058

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

1.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.039

Polyphen

0.96

Vest4

0.25

MVP

0.32

MPC

0.93

ClinPred

0.073

GERP RS

1.7

Varity_R

0.12

gMVP

0.44

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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