Variant 8-23116765-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_003841.5(TNFRSF10C):c.514C>T(p.Pro172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,579,142 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

TNFRSF10C
NM_003841.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0860

Variant links:

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]

TNFRSF10C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033526719).

BP6

Variant 8-23116765-C-T is Benign according to our data. Variant chr8-23116765-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658478.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5 linkuse as main transcript	c.514C>T	p.Pro172Ser	missense_variant	5/5	ENST00000356864.4	NP_003832.3	O14798

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNFRSF10C	ENST00000356864.4 linkuse as main transcript	c.514C>T	p.Pro172Ser	missense_variant	5/5	1	NM_003841.5	ENSP00000349324.4	O14798
TNFRSF10C	ENST00000517558.1 linkuse as main transcript	n.*204C>T		non_coding_transcript_exon_variant	4/4	2		ENSP00000428235.1	E5RJI1
TNFRSF10C	ENST00000517558.1 linkuse as main transcript	n.*204C>T		3_prime_UTR_variant	4/4	2		ENSP00000428235.1	E5RJI1

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

139

AN:

150078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.00164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000837

AC:

208

AN:

248464

Hom.:

AF XY:

0.000723

AC XY:

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000124

AC:

177

AN:

1428948

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

117

AN XY:

711316

show subpopulations

Gnomad4 AFR exome

AF:

0.0000910

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000938

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.0000932

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.000925

AC:

139

AN:

150194

Hom.:

Cov.:

AF XY:

0.000844

AC XY:

AN XY:

73430

show subpopulations

Gnomad4 AFR

AF:

0.000315

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000627

Gnomad4 FIN

AF:

0.00164

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00998

Hom.:

Bravo

AF:

0.00663

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00533

AC:

647

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

TNFRSF10C: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.3

DANN

Benign

0.56

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.44

REVEL

Benign

0.12

Sift

Benign

0.094

Sift4G

Benign

0.83

Polyphen

0.62

Vest4

0.081

MVP

0.39

MPC

0.015

ClinPred

0.0085

GERP RS

0.78

Varity_R

0.050

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over