Variant X-3615831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005044.5(PRKX):c.935C>T(p.Pro312Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,204,401 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.00017 ( 0 hom. 54 hem. )

Consequence

PRKX
NM_005044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKX	NM_005044.5 linkuse as main transcript	c.935C>T	p.Pro312Leu	missense_variant	7/9	ENST00000262848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKX	ENST00000262848.6 linkuse as main transcript	c.935C>T	p.Pro312Leu	missense_variant	7/9	1	NM_005044.5	P1
PRKX	ENST00000425240.1 linkuse as main transcript	n.637C>T		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000894

AC:

AN:

111870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34036

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

169533

Hom.:

AF XY:

0.0000899

AC XY:

AN XY:

55643

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000351

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

189

AN:

1092531

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

358759

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.000144

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.0000894

AC:

AN:

111870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34036

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.0000954

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.935C>T (p.P312L) alteration is located in exon 7 (coding exon 7) of the PRKX gene. This alteration results from a C to T substitution at nucleotide position 935, causing the proline (P) at amino acid position 312 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.23

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.27

Sift

Benign

0.54

Sift4G

Benign

0.71

Polyphen

0.027

Vest4

0.69

MVP

0.34

MPC

0.75

ClinPred

0.097

GERP RS

3.7

Varity_R

0.35

gMVP

0.64

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

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