chr9-37034026-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016734.3(PAX5):c.6T>A(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,605,240 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 17 hom. )

Consequence

PAX5
NM_016734.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 2.38

Publications

7 publications found

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:

EBLN3P (HGNC:50682): (endogenous Bornavirus like nucleoprotein 3, pseudogene)

EBLN3P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008341283).

BP6

Variant 9-37034026-A-T is Benign according to our data. Variant chr9-37034026-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 134997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00236 (351/148970) while in subpopulation EAS AF = 0.0107 (54/5034). AF 95% confidence interval is 0.00844. There are 7 homozygotes in GnomAd4. There are 227 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX5	NM_016734.3 link	c.6T>A	p.Asp2Glu	missense_variant	Exon 1 of 10	ENST00000358127.9	NP_057953.1	Q02548-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX5	ENST00000358127.9 link	c.6T>A	p.Asp2Glu	missense_variant	Exon 1 of 10	1	NM_016734.3	ENSP00000350844.4		Q02548-1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

352

AN:

148914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0107

Gnomad SAS

AF:

0.000429

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000428

Gnomad OTH

AF:

0.00196

GnomAD2 exomes

AF:

0.00327

AC:

809

AN:

247530

AF XY:

0.00313

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.0223

Gnomad NFE exome

AF:

0.000949

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00134

AC:

1949

AN:

1456270

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

931

AN XY:

724594

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33316

American (AMR)

AF:

0.0000224

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00710

AC:

280

AN:

39446

South Asian (SAS)

AF:

0.000280

AC:

AN:

85838

European-Finnish (FIN)

AF:

0.0225

AC:

1201

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4384

European-Non Finnish (NFE)

AF:

0.000260

AC:

288

AN:

1109098

Other (OTH)

AF:

0.00253

AC:

152

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

194

292

389

486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00236

AC:

351

AN:

148970

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

227

AN XY:

72478

show subpopulations

African (AFR)

AF:

0.000199

AC:

AN:

40144

American (AMR)

AF:

0.00

AC:

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.0107

AC:

AN:

5034

South Asian (SAS)

AF:

0.000430

AC:

AN:

4652

European-Finnish (FIN)

AF:

0.0263

AC:

255

AN:

9692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000428

AC:

AN:

67746

Other (OTH)

AF:

0.00146

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000829

Hom.:

Bravo

AF:

0.000570

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00295

AC:

358

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2024

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

not specified

Benign:1Other:1

Apr 28, 2020

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.81

T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0083

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

0.46

N;N;N;.;.;N;N;N;N

PhyloP100

2.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.23

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.35

T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;B;B;.;.;.;.

Vest4

0.25

MutPred

0.14

Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);

MVP

0.88

MPC

1.3

ClinPred

0.022

GERP RS

4.9

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.087

gMVP

0.56

Mutation Taster

=289/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over