8-23043187-CG-GC

Variant names:

• chr8-23043187-CG-GC
• NM_003842.5:c.200_201delCGinsGC
• TNFRSF10B p.Ala67Gly

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.200_201delCGinsGC​(p.Ala67Gly) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A67V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNFRSF10B NM_003842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 0 publications found

Genes affected

TNFRSF10B (HGNC:11905): (TNF receptor superfamily member 10b) The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]

TNFRSF10B Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003842.5. 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
	TNFRSF10B	NM_003842.5	MANE Select	c.200_201delCGinsGC	p.Ala67Gly	missense	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.200_201delCGinsGC	p.Ala67Gly	missense	N/A	NP_671716.2	O14763-2
	TNFRSF10B	NR_027140.2		n.282-12316_282-12315delCGinsGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.200_201delCGinsGC	p.Ala67Gly	missense	N/A	ENSP00000276431.4	O14763-1
	TNFRSF10B	ENST00000347739.3	TSL:1	c.200_201delCGinsGC	p.Ala67Gly	missense	N/A	ENSP00000317859.3	O14763-2
	TNFRSF10B	ENST00000931215.1		c.200_201delCGinsGC	p.Ala67Gly	missense	N/A	ENSP00000601274.1

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		-0.15

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: chr8-22900700;