rs765663059

Variant names:

• chr8-23022922-T-A
• NM_003842.5:c.1072A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-23022922-T-A
• chr8-23022922-T-C
• chr8-23022922-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003842.5(TNFRSF10B):​c.1072A>T​(p.Met358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNFRSF10B NM_003842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26624864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.1072A>T	p.Met358Leu	missense_variant	Exon 9 of 9	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.985A>T	p.Met329Leu	missense_variant	Exon 10 of 10		NP_671716.2
TNFRSF10B	NR_027140.2	n.1016A>T		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.1072A>T	p.Met358Leu	missense_variant	Exon 9 of 9	1	NM_003842.5	ENSP00000276431.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.2
DANN	Benign	0.56
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.57	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.074	T;T
Polyphen		0.038	B;P
Vest4		0.17
MutPred		0.57		Gain of helix (P = 0.0854);.;
MVP		0.69
MPC		0.059
ClinPred		0.11	T
GERP RS		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-22880435;