X-3713106-C-G

Variant names:

• chrX-3713106-C-G
• rs1363924841
• NM_005044.5:c.148G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005044.5(PRKX):​c.148G>C​(p.Asp50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 112,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PRKX NM_005044.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.821
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1766862).
• 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.148G>C	p.Asp50His	missense	Exon 1 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.148G>C	p.Asp50His	missense	Exon 1 of 9	ENSP00000262848.5	P51817
	PRKX	ENST00000910398.1		c.148G>C	p.Asp50His	missense	Exon 1 of 9	ENSP00000580457.1
	PRKX	ENST00000953311.1		c.148G>C	p.Asp50His	missense	Exon 1 of 9	ENSP00000623370.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 3 AN: 112929 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000641

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1053646 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 340834

African (AFR) AF: 0.00 AC: 0 AN: 23527

American (AMR) AF: 0.00 AC: 0 AN: 29433

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18242

East Asian (EAS) AF: 0.00 AC: 0 AN: 26124

South Asian (SAS) AF: 0.00 AC: 0 AN: 50389

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3982

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823253

Other (OTH) AF: 0.00 AC: 0 AN: 44468

GnomAD4 genome AF: 0.0000266 AC: 3 AN: 112929 Hom.: 0 Cov.: 24 AF XY: 0.0000570 AC XY: 2 AN XY: 35101

African (AFR) AF: 0.0000641 AC: 2 AN: 31182

American (AMR) AF: 0.00 AC: 0 AN: 10829

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3535

South Asian (SAS) AF: 0.00 AC: 0 AN: 2812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53199

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.00000756

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	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.82
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.044
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.053	T
Polyphen		0.88	P
Vest4		0.10
MutPred		0.35		Gain of catalytic residue at L52 (P = 0.0711)
MVP		0.30
MPC		0.91
ClinPred		0.29	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.41
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs1363924841; hg19: chrX-3631147;