Variant rs758368747 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000358127.9(PAX5):c.435G>C(p.Gln145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PAX5
ENST00000358127.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.772

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:

LOC105376032 (HGNC:):

LOC105376032 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX5	NM_016734.3 linkuse as main transcript	c.435G>C	p.Gln145His	missense_variant	4/10	ENST00000358127.9	NP_057953.1
LOC105376032	XR_007061476.1 linkuse as main transcript	n.932C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX5	ENST00000358127.9 linkuse as main transcript	c.435G>C	p.Gln145His	missense_variant	4/10	1	NM_016734.3	ENSP00000350844	P1	Q02548-1
	ENST00000509911.3 linkuse as main transcript	n.195-937C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acute lymphoid leukemia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.71

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

M;M;M;.;.;M;.;.;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.0

D;D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.97

D;.;.;D;D;.;.;.;.;.;.

Vest4

0.60

MutPred

0.21

Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);.;.;.;Loss of MoRF binding (P = 0.1118);Loss of MoRF binding (P = 0.1118);

MVP

0.99

MPC

2.4

ClinPred

0.99

GERP RS

3.5

Varity_R

0.62

gMVP

0.72

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