17-7559152-CT-TC

Variant names:

• chr17-7559152-CT-TC
• NM_003808.4:c.113_114delCTinsTC
• TNFSF13 p.Ala38Val

Variant summary

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

The NM_003808.4(TNFSF13):​c.113_114delCTinsTC​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

ENSG00000276384 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003808.4. 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
	TNFSF13	NM_003808.4	MANE Select	c.113_114delCTinsTC	p.Ala38Val	missense	N/A	NP_003799.1	O75888-1
	TNFSF13	NM_172088.4		c.113_114delCTinsTC	p.Ala38Val	missense	N/A	NP_742085.1	O75888-3
	TNFSF13	NM_172087.3		c.113_114delCTinsTC	p.Ala38Val	missense	N/A	NP_742084.1	O75888-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF13	ENST00000338784.9	TSL:1 MANE Select	c.113_114delCTinsTC	p.Ala38Val	missense	N/A	ENSP00000343505.4	O75888-1
	TNFSF13	ENST00000396545.4	TSL:1	c.113_114delCTinsTC	p.Ala38Val	missense	N/A	ENSP00000379794.4	O75888-3
	TNFSF13	ENST00000349228.8	TSL:1	c.113_114delCTinsTC	p.Ala38Val	missense	N/A	ENSP00000314455.6	O75888-2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

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: chr17-7462469;