9-36846916-G-C

Position:

• chr9-36846916-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001280549.2(PAX5):​c.794C>G​(p.Pro265Arg) 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. 9/15 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: 33)
• Consequence: PAX5 NM_001280549.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

PAX5 (HGNC:8619): (paired box 5) This gene encodes a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly conserved DNA-binding motif, known as the paired box. Paired box transcription factors are important regulators in early development, and alterations in the expression of their genes are thought to contribute to neoplastic transformation. This gene encodes the B-cell lineage specific activator protein that is expressed at early, but not late stages of B-cell differentiation. Its expression has also been detected in developing CNS and testis and so the encoded protein may also play a role in neural development and spermatogenesis. This gene is located at 9p13, which is involved in t(9;14)(p13;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype, and in derived large-cell lymphomas. This translocation brings the potent E-mu enhancer of the IgH gene into close proximity of the PAX5 promoter, suggesting that the deregulation of transcription of this gene contributes to the pathogenesis of these lymphomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

PAX5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14888704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX5	NM_016734.3	c.1026C>G	p.Ser342Ser	synonymous_variant	9/10	ENST00000358127.9	NP_057953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX5	ENST00000358127.9	c.1026C>G	p.Ser342Ser	synonymous_variant	9/10	1	NM_016734.3	ENSP00000350844.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	0.47
DANN	Benign	0.95
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.45
Sift	Benign	0.076	T
Sift4G	Uncertain	0.012	D
Polyphen		0.0	B
Vest4		0.35
MutPred		0.26		Gain of catalytic residue at P265 (P = 0.0373);
MVP		0.59
ClinPred		0.10	T
GERP RS		-4.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr9-36846913;