ENST00000523241.6:c.878C>T

Variant names:

Variant summary

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

The ENST00000523241.6(PAX5):c.878C>T(p.Thr293Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 1,570,902 control chromosomes in the GnomAD database, including 662,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T293A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.78 ( 50582 hom., cov: 30)

Exomes 𝑓: 0.92 ( 612290 hom. )

Consequence

PAX5
ENST00000523241.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.626

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8845094E-7).

BP6

Variant 9-36840626-G-A is Benign according to our data. Variant chr9-36840626-G-A is described in ClinVar as [Benign]. Clinvar id is 134998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX5	NM_016734.3 link	c.1110C>T	p.Tyr370Tyr	synonymous_variant	Exon 10 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.1110C>T	p.Tyr370Tyr	synonymous_variant	Exon 10 of 10	1	NM_016734.3	ENSP00000350844.4		Q02548-1

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118283

AN:

151938

Hom.:

50567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.864

Gnomad ASJ

AF:

0.886

Gnomad EAS

AF:

0.892

Gnomad SAS

AF:

0.848

Gnomad FIN

AF:

0.954

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.823

GnomAD3 exomes

AF:

0.878

AC:

159748

AN:

181860

Hom.:

71852

AF XY:

0.886

AC XY:

85859

AN XY:

96856

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.869

Gnomad ASJ exome

AF:

0.889

Gnomad EAS exome

AF:

0.880

Gnomad SAS exome

AF:

0.858

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.944

Gnomad OTH exome

AF:

0.902

GnomAD4 exome

AF:

0.924

AC:

1311334

AN:

1418846

Hom.:

612290

Cov.:

AF XY:

0.924

AC XY:

648215

AN XY:

701494

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

0.898

Gnomad4 SAS exome

AF:

0.861

Gnomad4 FIN exome

AF:

0.951

Gnomad4 NFE exome

AF:

0.951

Gnomad4 OTH exome

AF:

0.892

GnomAD4 genome

AF:

0.778

AC:

118328

AN:

152056

Hom.:

50582

Cov.:

AF XY:

0.783

AC XY:

58210

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.864

Gnomad4 ASJ

AF:

0.886

Gnomad4 EAS

AF:

0.892

Gnomad4 SAS

AF:

0.849

Gnomad4 FIN

AF:

0.954

Gnomad4 NFE

AF:

0.947

Gnomad4 OTH

AF:

0.826

Alfa

AF:

0.909

Hom.:

94527

Bravo

AF:

0.753

TwinsUK

AF:

0.950

AC:

3522

ALSPAC

AF:

0.951

AC:

3664

ESP6500AA

AF:

0.421

AC:

1839

ESP6500EA

AF:

0.938

AC:

8019

ExAC

AF:

0.847

AC:

95959

Asia WGS

AF:

0.846

AC:

2943

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Other:1

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

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Pathogenic

0.21

CADD

Benign

6.3

DANN

Uncertain

0.98

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

6.9e-7

T;T

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.81

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.21

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0

B;B

Vest4

0.19

ClinPred

0.0065

GERP RS

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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