Variant X-3615805-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005044.5(PRKX):c.951+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,193,789 control chromosomes in the GnomAD database, including 34 homozygotes. There are 813 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., 366 hem., cov: 23)

Exomes 𝑓: 0.0015 ( 15 hom. 447 hem. )

Consequence

PRKX
NM_005044.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.278

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-3615805-T-A is Benign according to our data. Variant chrX-3615805-T-A is described in ClinVar as [Benign]. Clinvar id is 777784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1337/112089) while in subpopulation AFR AF= 0.0406 (1255/30905). AF 95% confidence interval is 0.0387. There are 19 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKX	NM_005044.5 linkuse as main transcript	c.951+10A>T		intron_variant		ENST00000262848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKX	ENST00000262848.6 linkuse as main transcript	c.951+10A>T		intron_variant		1	NM_005044.5	P1
PRKX	ENST00000425240.1 linkuse as main transcript	n.653+10A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1329

AN:

112036

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

358

AN XY:

34194

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00437

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0209

Gnomad NFE

AF:

0.000394

Gnomad OTH

AF:

0.00600

GnomAD3 exomes

AF:

0.00364

AC:

573

AN:

157500

Hom.:

AF XY:

0.00232

AC XY:

111

AN XY:

47932

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000702

Gnomad NFE exome

AF:

0.000311

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00154

AC:

1668

AN:

1081700

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

447

AN XY:

350798

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.00214

Gnomad4 ASJ exome

AF:

0.0000523

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.0000251

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.0119

AC:

1337

AN:

112089

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

366

AN XY:

34257

show subpopulations

Gnomad4 AFR

AF:

0.0406

Gnomad4 AMR

AF:

0.00437

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000394

Gnomad4 OTH

AF:

0.00592

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.59

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over