8-23111803-C-G

Variant names:

• chr8-23111803-C-G
• rs1280095392
• ENST00000520607.1:c.-98C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000520607.1(ENSG00000284956):​c.-98C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENSG00000284956 ENST00000520607.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 0 publications found

Genes affected

ENSG00000284956 (HGNC:):

TNFRSF10C (HGNC:11906): (TNF receptor superfamily member 10c) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026910782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520607.1. 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
	TNFRSF10C	NM_003841.5	MANE Select	c.144C>G	p.Phe48Leu	missense	Exon 2 of 5	NP_003832.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-98C>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 6	ENSP00000493787.1	A0A2R8YDH7
	TNFRSF10C	ENST00000356864.4	TSL:1 MANE Select	c.144C>G	p.Phe48Leu	missense	Exon 2 of 5	ENSP00000349324.4	O14798
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-98C>G		5_prime_UTR	Exon 4 of 6	ENSP00000493787.1	A0A2R8YDH7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.53
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.42
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.077
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.062
MutPred		0.27		Loss of methylation at K49 (P = 0.0273)
MVP		0.21
MPC		0.0073
ClinPred		0.057	T
GERP RS		-0.48
Varity_R		0.062
gMVP		0.53
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1280095392; hg19: chr8-22969316;