5-109378292-C-G

Position:

• chr5-109378292-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014819.5(PJA2):​c.1195G>C​(p.Gly399Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PJA2 NM_014819.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.830

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]

ACMG classification

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=0.058932304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PJA2	NM_014819.5	c.1195G>C	p.Gly399Arg	missense_variant	4/10	ENST00000361189.7	NP_055634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PJA2	ENST00000361189.7	c.1195G>C	p.Gly399Arg	missense_variant	4/10	1	NM_014819.5	ENSP00000354775.2
PJA2	ENST00000361557.4	c.1195G>C	p.Gly399Arg	missense_variant	3/9	2		ENSP00000355284.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.1195G>C (p.G399R) alteration is located in exon 4 (coding exon 3) of the PJA2 gene. This alteration results from a G to C substitution at nucleotide position 1195, causing the glycine (G) at amino acid position 399 to be replaced by an arginine (R). 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	Benign	0.079
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0051
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0010	B;B
Vest4		0.088
MutPred		0.12		Gain of methylation at G399 (P = 0.0254);Gain of methylation at G399 (P = 0.0254);
MVP		0.23
MPC		0.0097
ClinPred		0.082	T
GERP RS		4.6
Varity_R		0.044
gMVP		0.082

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-108713993;