Variant 5-109368693-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014819.5(PJA2):c.1337G>A(p.Gly446Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

PJA2
NM_014819.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025113553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PJA2	NM_014819.5 linkuse as main transcript	c.1337G>A	p.Gly446Asp	missense_variant	5/10	ENST00000361189.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PJA2	ENST00000361189.7 linkuse as main transcript	c.1337G>A	p.Gly446Asp	missense_variant	5/10	1	NM_014819.5	P1	O43164-1
PJA2	ENST00000361557.4 linkuse as main transcript	c.1337G>A	p.Gly446Asp	missense_variant	4/9	2		P1	O43164-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251250

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000824

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

Dec 06, 2022

The c.1337G>A (p.G446D) alteration is located in exon 5 (coding exon 4) of the PJA2 gene. This alteration results from a G to A substitution at nucleotide position 1337, causing the glycine (G) at amino acid position 446 to be replaced by an aspartic acid (D). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.026

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.012

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

N;N

MutationTaster

Benign

0.76

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.16

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.34

B;B

Vest4

0.58

MutPred

0.095

Loss of glycosylation at S445 (P = 0.0395);Loss of glycosylation at S445 (P = 0.0395);

MVP

0.23

MPC

0.052

ClinPred

0.043

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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