X-3655393-C-T
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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
NM_005044.5 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.88
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 |
---|---|---|---|---|---|---|---|
PRKX | NM_005044.5 | c.355G>A | p.Glu119Lys | missense_variant | 3/9 | ENST00000262848.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKX | ENST00000262848.6 | c.355G>A | p.Glu119Lys | missense_variant | 3/9 | 1 | NM_005044.5 | P1 | |
PRKX | ENST00000425240.1 | n.57G>A | non_coding_transcript_exon_variant | 2/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 17AN: 112670Hom.: 0 Cov.: 23 AF XY: 0.000115 AC XY: 4AN XY: 34822
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GnomAD3 exomes AF: 0.000209 AC: 38AN: 182104Hom.: 0 AF XY: 0.000194 AC XY: 13AN XY: 66956
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GnomAD4 exome AF: 0.000213 AC: 234AN: 1098154Hom.: 0 Cov.: 32 AF XY: 0.000220 AC XY: 80AN XY: 363522
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GnomAD4 genome AF: 0.000151 AC: 17AN: 112721Hom.: 0 Cov.: 23 AF XY: 0.000115 AC XY: 4AN XY: 34883
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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 | Jul 06, 2021 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at