X-3656497-A-G

Variant names:

• chrX-3656497-A-G
• rs17335275
• NM_005044.5:c.336-1085T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005044.5(PRKX):​c.336-1085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 110,384 control chromosomes in the GnomAD database, including 4,439 homozygotes. There are 10,196 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (4439 hom., 10196 hem., cov: 22)
• Consequence: PRKX NM_005044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKX	NM_005044.5	c.336-1085T>C		intron_variant	Intron 2 of 8	ENST00000262848.6	NP_005035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKX	ENST00000262848.6	c.336-1085T>C		intron_variant	Intron 2 of 8	1	NM_005044.5	ENSP00000262848.5
PRKX	ENST00000425240.1	n.38-1085T>C		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 35241 AN: 110332 Hom.: 4428 Cov.: 22 AF XY: 0.311 AC XY: 10164 AN XY: 32672

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 35288 AN: 110384 Hom.: 4439 Cov.: 22 AF XY: 0.311 AC XY: 10196 AN XY: 32734

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.388

Alfa AF: 0.326 Hom.: 4247

Bravo AF: 0.338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.13

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

LitVar

Other links and lift over

dbSNP: rs17335275; hg19: chrX-3574538;