9-36840620-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001280549.2(PAX5):c.884T>C(p.Ile295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,576,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PAX5
NM_001280549.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.58

Publications

1 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 Gene-Disease associations (from GenCC):

leukemia, acute lymphoblastic, susceptibility to, 3
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Broad Center for Mendelian Genomics
PAX5-related B lymphopenia and autism spectrum disorder
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

PAX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014026582).

BP6

Variant 9-36840620-A-G is Benign according to our data. Variant chr9-36840620-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 3414554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001280549.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAX5	NM_016734.3	MANE Select	c.1116T>C	p.Tyr372Tyr	synonymous	Exon 10 of 10	NP_057953.1	Q02548-1
PAX5	NM_001280549.2		c.884T>C	p.Ile295Thr	missense	Exon 8 of 8	NP_001267478.1	E7EQT0
PAX5	NM_001280550.2		c.797T>C	p.Ile266Thr	missense	Exon 7 of 7	NP_001267479.1	E7ERW5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAX5	ENST00000523241.6	TSL:1	c.884T>C	p.Ile295Thr	missense	Exon 8 of 8	ENSP00000429637.1	E7EQT0
PAX5	ENST00000520154.6	TSL:1	c.797T>C	p.Ile266Thr	missense	Exon 7 of 7	ENSP00000429291.1	E7ERW5
PAX5	ENST00000358127.9	TSL:1 MANE Select	c.1116T>C	p.Tyr372Tyr	synonymous	Exon 10 of 10	ENSP00000350844.4	Q02548-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000545

AC:

AN:

183432

AF XY:

0.0000512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000374

Gnomad ASJ exome

AF:

0.000798

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1424244

Hom.:

Cov.:

AF XY:

0.0000185

AC XY:

AN XY:

704528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33236

American (AMR)

AF:

0.0000526

AC:

AN:

38028

Ashkenazi Jewish (ASJ)

AF:

0.000631

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

38446

South Asian (SAS)

AF:

0.00

AC:

AN:

81038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49636

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000549

AC:

AN:

1093636

Other (OTH)

AF:

0.0000507

AC:

AN:

59146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000971

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000510

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

7.4

(source)

DANN

Benign

0.15

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.39

M_CAP

Benign

0.084

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.12

PhyloP100

2.6

PROVEAN

Benign

2.1

REVEL

Uncertain

0.38

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.22

Gain of glycosylation at I295 (P = 7e-04)

MVP

0.41

ClinPred

0.12

GERP RS

4.4

Mutation Taster

=72/28

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over