X-3655393-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005044.5(PRKX):​c.355G>A​(p.Glu119Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000207 in 1,210,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 84 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 4 hem., cov: 23)
Exomes 𝑓: 0.00021 ( 0 hom. 80 hem. )

Consequence

PRKX
NM_005044.5 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.060579777).
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKXNM_005044.5 linkuse as main transcriptc.355G>A p.Glu119Lys missense_variant 3/9 ENST00000262848.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKXENST00000262848.6 linkuse as main transcriptc.355G>A p.Glu119Lys missense_variant 3/91 NM_005044.5 P1
PRKXENST00000425240.1 linkuse as main transcriptn.57G>A non_coding_transcript_exon_variant 2/75

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
17
AN:
112670
Hom.:
0
Cov.:
23
AF XY:
0.000115
AC XY:
4
AN XY:
34822
show subpopulations
Gnomad AFR
AF:
0.0000322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000282
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000481
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000169
Gnomad OTH
AF:
0.000664
GnomAD3 exomes
AF:
0.000209
AC:
38
AN:
182104
Hom.:
0
AF XY:
0.000194
AC XY:
13
AN XY:
66956
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00113
Gnomad NFE exome
AF:
0.000235
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000213
AC:
234
AN:
1098154
Hom.:
0
Cov.:
32
AF XY:
0.000220
AC XY:
80
AN XY:
363522
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00178
Gnomad4 NFE exome
AF:
0.000178
Gnomad4 OTH exome
AF:
0.000217
GnomAD4 genome
AF:
0.000151
AC:
17
AN:
112721
Hom.:
0
Cov.:
23
AF XY:
0.000115
AC XY:
4
AN XY:
34883
show subpopulations
Gnomad4 AFR
AF:
0.0000321
Gnomad4 AMR
AF:
0.000282
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000481
Gnomad4 NFE
AF:
0.000169
Gnomad4 OTH
AF:
0.000655
Alfa
AF:
0.000192
Hom.:
8
Bravo
AF:
0.000125
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00104
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.000231
AC:
28
EpiCase
AF:
0.000327
EpiControl
AF:
0.000237

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 submitterclinical testingAmbry GeneticsJul 06, 2021The c.355G>A (p.E119K) alteration is located in exon 3 (coding exon 3) of the PRKX gene. This alteration results from a G to A substitution at nucleotide position 355, causing the glutamic acid (E) at amino acid position 119 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.41
N
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.066
Sift
Benign
0.13
T
Sift4G
Benign
0.35
T
Polyphen
0.64
P
Vest4
0.43
MVP
0.33
MPC
0.85
ClinPred
0.12
T
GERP RS
3.4
Varity_R
0.23
gMVP
0.59

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.

Other links and lift over

dbSNP: rs200883737; hg19: chrX-3573434; API