Variant chr5-109356003-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014819.5(PJA2):c.1676G>C(p.Gly559Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,556 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PJA2
NM_014819.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

Variant links:

Genes affected

PJA2 (HGNC:17481): (praja ring finger ubiquitin ligase 2) Enables protein kinase A catalytic subunit binding activity; protein kinase A regulatory subunit binding activity; and ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of macrophage activation; and regulation of signal transduction. Located in cytoplasm; intermediate filament cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PJA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PJA2	NM_014819.5 linkuse as main transcript	c.1676G>C	p.Gly559Ala	missense_variant	7/10	ENST00000361189.7	NP_055634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PJA2	ENST00000361189.7 linkuse as main transcript	c.1676G>C	p.Gly559Ala	missense_variant	7/10	1	NM_014819.5	ENSP00000354775.2		O43164-1
PJA2	ENST00000361557.4 linkuse as main transcript	c.1676G>C	p.Gly559Ala	missense_variant	6/9	2		ENSP00000355284.3		O43164-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250780

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135542

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461096

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73936

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

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

Nov 17, 2022

The c.1676G>C (p.G559A) alteration is located in exon 7 (coding exon 6) of the PJA2 gene. This alteration results from a G to C substitution at nucleotide position 1676, causing the glycine (G) at amino acid position 559 to be replaced by an alanine (A). 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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

1.0

D;D

Vest4

0.73

MVP

0.50

MPC

0.062

ClinPred

0.98

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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