Variant chr9-36840449-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.308

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PAX5	NM_016734.3 linkuse as main transcript	c.*111C>T		3_prime_UTR_variant	10/10	ENST00000358127.9	NP_057953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX5	ENST00000358127.9 linkuse as main transcript	c.*111C>T		3_prime_UTR_variant	10/10	1	NM_016734.3	ENSP00000350844	P1	Q02548-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3637

AN:

152158

Hom.:

100

Cov.:

show subpopulations

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.:

AF XY:

0.0330

AC XY:

15248

AN XY:

462480

show subpopulations

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.:

AF XY:

0.0267

AC XY:

1989

AN XY:

74456

show subpopulations

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.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0950

AC:

329

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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