TONSL p.Leu456Leu

Variant names:

• chr8-144440132-G-G
• NM_013432.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr8-144440133--
• chr8-144440135-G-A
• chr8-144440133-T-A
• chr8-144440133-T-G
• chr8-144440133-T-C
• chr8-144440133-TAG-CAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013432.5(TONSL):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TONSL NM_013432.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

TONSL (HGNC:7801): (tonsoku like, DNA repair protein) The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus. [provided by RefSeq, Jul 2008]

TONSL-AS1 (HGNC:51556): (TONSL antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013432.5. 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
	TONSL	NM_013432.5	MANE Select	c.		exon_region	Exon 11 of 26	NP_038460.4
	TONSL-AS1	NR_109770.1		n.		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TONSL	ENST00000409379.8	TSL:1 MANE Select	c.		exon_region	Exon 11 of 26	ENSP00000386239.3	Q96HA7-1
	TONSL	ENST00000932056.1		c.		exon_region	Exon 11 of 27	ENSP00000602115.1
	TONSL	ENST00000971177.1		c.		exon_region	Exon 11 of 26	ENSP00000641236.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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: chr8-145665515;