8-23111578-T-G

Variant names:

• chr8-23111578-T-G
• rs10111172
• NM_003841.5:c.61-142T>G

Variant summary

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

The NM_003841.5(TNFRSF10C):​c.61-142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 534,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 29)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: TNFRSF10C NM_003841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 0 publications found

Genes affected

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]

ENSG00000284956 (HGNC:):

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 (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003841.5. 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
	TNFRSF10C	NM_003841.5	MANE Select	c.61-142T>G		intron	N/A	NP_003832.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10C	ENST00000356864.4	TSL:1 MANE Select	c.61-142T>G		intron	N/A	ENSP00000349324.4	O14798
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-181-142T>G		intron	N/A	ENSP00000493787.1	A0A2R8YDH7
	TNFRSF10C	ENST00000877636.1		c.61-142T>G		intron	N/A	ENSP00000547695.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000936 AC: 5 AN: 534144 Hom.: 0 AF XY: 0.0000105 AC XY: 3 AN XY: 285274

African (AFR) AF: 0.00 AC: 0 AN: 14042

American (AMR) AF: 0.00 AC: 0 AN: 26338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16244

East Asian (EAS) AF: 0.00 AC: 0 AN: 30318

South Asian (SAS) AF: 0.00 AC: 0 AN: 53432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3778

European-Non Finnish (NFE) AF: 0.0000158 AC: 5 AN: 316396

Other (OTH) AF: 0.00 AC: 0 AN: 28718

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.38
PhyloP100		-1.7

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

Other links and lift over

dbSNP: rs10111172; hg19: chr8-22969091;