9-36840449-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016734.3(PAX5):c.*111C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,050,558 control chromosomes in the GnomAD database, including 1,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (100 hom., cov: 32)
  • Exomes 𝑓: 0.030 (1006 hom.)
• Consequence: PAX5 NM_016734.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.308

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-36840449-G-A is Benign according to our data. Variant chr9-36840449-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1254811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX5	NM_016734.3	c.*111C>T		3_prime_UTR_variant	10/10	ENST00000358127.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX5	ENST00000358127.9	c.*111C>T		3_prime_UTR_variant	10/10	1	NM_016734.3	P1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3637 AN: 152158 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0296 AC: 26605 AN: 898282 Hom.: 1006 Cov.: 12 AF XY: 0.0330 AC XY: 15248 AN XY: 462480

Gnomad4 AFR exome AF: 0.00945

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.0999

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0347

GnomAD4 genome AF: 0.0239 AC: 3635 AN: 152276 Hom.: 100 Cov.: 32 AF XY: 0.0267 AC XY: 1989 AN XY: 74456

Gnomad4 AFR AF: 0.00844

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0206 Hom.: 58

Bravo AF: 0.0264

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.9
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs3739437; hg19: chr9-36840446; COSMIC: COSV63905038; COSMIC: COSV63905038;