Variant X-3612334-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005044.5(PRKX):c.952-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,204,527 control chromosomes in the GnomAD database, including 4 homozygotes. There are 999 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., 44 hem., cov: 22)

Exomes 𝑓: 0.0027 ( 4 hom. 955 hem. )

Consequence

PRKX
NM_005044.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008753

Clinical Significance

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

Conservation

PhyloP100: -1.64

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-3612334-C-T is Benign according to our data. Variant chrX-3612334-C-T is described in ClinVar as [Benign]. Clinvar id is 784728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKX	NM_005044.5 linkuse as main transcript	c.952-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKX	ENST00000262848.6 linkuse as main transcript	c.952-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005044.5	P1
PRKX	ENST00000425240.1 linkuse as main transcript	n.654-9G>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

201

AN:

110888

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33102

show subpopulations

Gnomad AFR

AF:

0.000361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00117

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000773

Gnomad FIN

AF:

0.000677

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00534

GnomAD3 exomes

AF:

0.00176

AC:

307

AN:

174571

Hom.:

AF XY:

0.00164

AC XY:

AN XY:

59627

show subpopulations

Gnomad AFR exome

AF:

0.000545

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00268

AC:

2927

AN:

1093583

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

955

AN XY:

359263

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00170

Gnomad4 FIN exome

AF:

0.000845

Gnomad4 NFE exome

AF:

0.00314

Gnomad4 OTH exome

AF:

0.00274

GnomAD4 genome

AF:

0.00181

AC:

201

AN:

110944

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33168

show subpopulations

Gnomad4 AFR

AF:

0.000360

Gnomad4 AMR

AF:

0.00117

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000775

Gnomad4 FIN

AF:

0.000677

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00527

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00153

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	Oct 06, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.014

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.038

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

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