3-172523334-CAC-TAA

Variant names:

• chr3-172523334-CAC-TAA
• NM_003810.4:c.49_51delGTGinsTTA
• TNFSF10 p.Val17Leu

Variant summary

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

The NM_003810.4(TNFSF10):​c.49_51delGTGinsTTA​(p.Val17Leu) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFSF10 NM_003810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 0 publications found

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. 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
	TNFSF10	NM_003810.4	MANE Select	c.49_51delGTGinsTTA	p.Val17Leu	missense	N/A	NP_003801.1	Q6IBA9
	TNFSF10	NM_001190942.2		c.49_51delGTGinsTTA	p.Val17Leu	missense	N/A	NP_001177871.1	P50591-2
	TNFSF10	NM_001190943.2		c.49_51delGTGinsTTA	p.Val17Leu	missense	N/A	NP_001177872.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.49_51delGTGinsTTA	p.Val17Leu	missense	N/A	ENSP00000241261.2	P50591-1
	TNFSF10	ENST00000420541.6	TSL:1	c.49_51delGTGinsTTA	p.Val17Leu	missense	N/A	ENSP00000389931.2	P50591-2
	TNFSF10	ENST00000466777.1	TSL:1	n.132_134delGTGinsTTA		non_coding_transcript_exon	Exon 1 of 2

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		0.89

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: chr3-172241124;