9-36966690-CGA-TAG

Variant names:

• chr9-36966690-CGA-TAG
• NM_016734.3:c.637_639delTCGinsCTA
• PAX5 p.Ser213Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016734.3(PAX5):​c.637_639delTCGinsCTA​(p.Ser213Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. S213S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAX5 NM_016734.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016734.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX5	NM_016734.3	MANE Select	c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	NP_057953.1	Q02548-1
	PAX5	NM_001280548.2		c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	NP_001267477.1	Q02548-2
	PAX5	NM_001280547.2		c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	NP_001267476.1	Q02548-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX5	ENST00000358127.9	TSL:1 MANE Select	c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	ENSP00000350844.4	Q02548-1
	PAX5	ENST00000377853.6	TSL:1	c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	ENSP00000367084.2	Q02548-2
	PAX5	ENST00000377852.7	TSL:1	c.637_639delTCGinsCTA	p.Ser213Leu	missense	N/A	ENSP00000367083.2	Q02548-6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-36966687;