rs150699468

Variant names:

• chrX-3615864-C-T
• rs150699468
• NM_005044.5:c.902G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005044.5(PRKX):​c.902G>A​(p.Arg301Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,206,113 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 68 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R301W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00016 (0 hom. 66 hem.)
• Consequence: PRKX NM_005044.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 2 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.902G>A	p.Arg301Gln	missense	Exon 7 of 9	NP_005035.1	P51817

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKX	ENST00000262848.6	TSL:1 MANE Select	c.902G>A	p.Arg301Gln	missense	Exon 7 of 9	ENSP00000262848.5	P51817
	PRKX	ENST00000910398.1		c.902G>A	p.Arg301Gln	missense	Exon 7 of 9	ENSP00000580457.1
	PRKX	ENST00000953311.1		c.902G>A	p.Arg301Gln	missense	Exon 7 of 9	ENSP00000623370.1

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 14 AN: 111492 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

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: 0.000170

Gnomad OTH AF: 0.000668

GnomAD2 exomes AF: 0.000218 AC: 38 AN: 174367 AF XY: 0.000168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.000458

GnomAD4 exome AF: 0.000164 AC: 179 AN: 1094621 Hom.: 0 Cov.: 29 AF XY: 0.000183 AC XY: 66 AN XY: 360287

African (AFR) AF: 0.0000759 AC: 2 AN: 26360

American (AMR) AF: 0.000544 AC: 19 AN: 34940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19314

East Asian (EAS) AF: 0.00 AC: 0 AN: 30141

South Asian (SAS) AF: 0.000338 AC: 18 AN: 53220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.000162 AC: 136 AN: 840178

Other (OTH) AF: 0.0000870 AC: 4 AN: 45985

GnomAD4 genome AF: 0.000126 AC: 14 AN: 111492 Hom.: 0 Cov.: 23 AF XY: 0.0000594 AC XY: 2 AN XY: 33698

African (AFR) AF: 0.0000651 AC: 2 AN: 30730

American (AMR) AF: 0.000192 AC: 2 AN: 10425

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2619

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000170 AC: 9 AN: 53082

Other (OTH) AF: 0.000668 AC: 1 AN: 1497

Alfa AF: 0.000356 Hom.: 2

Bravo AF: 0.000128

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000907 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.60	N
PhyloP100		5.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.31
Sift	Benign	0.030	D
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.24
MVP		0.73
MPC		0.98
ClinPred		0.15	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.51
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs150699468; hg19: chrX-3533905;