Variant rs246105 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014819.5(PJA2):c.2113G>A(p.Ala705Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,554 control chromosomes in the GnomAD database, including 54,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4816 hom., cov: 31)

Exomes 𝑓: 0.25 ( 50123 hom. )

Consequence

PJA2
NM_014819.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7231032E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PJA2	NM_014819.5 linkuse as main transcript	c.2113G>A	p.Ala705Thr	missense_variant	10/10	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.2113G>A	p.Ala705Thr	missense_variant	10/10	1	NM_014819.5	ENSP00000354775	P1	O43164-1
PJA2	ENST00000361557.4 linkuse as main transcript	c.2113G>A	p.Ala705Thr	missense_variant	9/9	2		ENSP00000355284	P1	O43164-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35810

AN:

151656

Hom.:

4810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.276

AC:

69320

AN:

250916

Hom.:

10966

AF XY:

0.278

AC XY:

37646

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.603

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.252

AC:

367541

AN:

1460780

Hom.:

50123

Cov.:

AF XY:

0.254

AC XY:

184412

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.236

AC:

35835

AN:

151774

Hom.:

4816

Cov.:

AF XY:

0.243

AC XY:

18030

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.588

Gnomad4 SAS

AF:

0.336

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.241

Hom.:

9524

Bravo

AF:

0.230

TwinsUK

AF:

0.230

AC:

852

ALSPAC

AF:

0.233

AC:

899

ESP6500AA

AF:

0.162

AC:

713

ESP6500EA

AF:

0.234

AC:

2016

ExAC

AF:

0.276

AC:

33456

Asia WGS

AF:

0.491

AC:

1705

AN:

3478

EpiCase

AF:

0.241

EpiControl

AF:

0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.000017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.063

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.0

B;B

Vest4

0.033

MPC

0.99

ClinPred

0.015

GERP RS

0.45

Varity_R

0.024

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over