chrX-3655393-C-T

Variant names:

• chrX-3655393-C-T
• rs200883737
• NM_005044.5:c.355G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKX	NM_005044.5	MANE Select	c.355G>A	p.Glu119Lys	missense	Exon 3 of 9	NP_005035.1	P51817

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKX	ENST00000262848.6	TSL:1 MANE Select	c.355G>A	p.Glu119Lys	missense	Exon 3 of 9	ENSP00000262848.5	P51817
	PRKX	ENST00000910398.1		c.355G>A	p.Glu119Lys	missense	Exon 3 of 9	ENSP00000580457.1
	PRKX	ENST00000953311.1		c.355G>A	p.Glu119Lys	missense	Exon 3 of 9	ENSP00000623370.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 17 AN: 112670 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.000209 AC: 38 AN: 182104 AF XY: 0.000194

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 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

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54124

European-Finnish (FIN) AF: 0.00178 AC: 72 AN: 40507

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.000178 AC: 150 AN: 842107

Other (OTH) AF: 0.000217 AC: 10 AN: 46089

GnomAD4 genome AF: 0.000151 AC: 17 AN: 112721 Hom.: 0 Cov.: 23 AF XY: 0.000115 AC XY: 4 AN XY: 34883

African (AFR) AF: 0.0000321 AC: 1 AN: 31109

American (AMR) AF: 0.000282 AC: 3 AN: 10657

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3573

South Asian (SAS) AF: 0.00 AC: 0 AN: 2742

European-Finnish (FIN) AF: 0.000481 AC: 3 AN: 6235

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53322

Other (OTH) AF: 0.000655 AC: 1 AN: 1526

Alfa AF: 0.000177 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.9
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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs200883737; hg19: chrX-3573434;