Variant 8-23114715-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003841.5(TNFRSF10C):c.225C>T(p.Tyr75Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,613,952 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 9 hom., cov: 32)

Exomes 𝑓: 0.013 ( 149 hom. )

Consequence

TNFRSF10C
NM_003841.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

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:

ENSG00000284956 (HGNC:):

ENSG00000284956 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 8-23114715-C-T is Benign according to our data. Variant chr8-23114715-C-T is described in ClinVar as [Benign]. Clinvar id is 717706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.27 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5 linkuse as main transcript	c.225C>T	p.Tyr75Tyr	synonymous_variant	3/5	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.225C>T	p.Tyr75Tyr	synonymous_variant	3/5	1	NM_003841.5	ENSP00000349324.4	O14798
ENSG00000284956	ENST00000520607 linkuse as main transcript	c.-17C>T		5_prime_UTR_variant	5/6	4		ENSP00000493787.1	A0A2R8YDH7
TNFRSF10C	ENST00000517558.1 linkuse as main transcript	n.119C>T		non_coding_transcript_exon_variant	2/4	2		ENSP00000428235.1	E5RJI1
TNFRSF10C	ENST00000518135.1 linkuse as main transcript	n.209C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00822

AC:

1251

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00814

AC:

2047

AN:

251488

Hom.:

AF XY:

0.00817

AC XY:

1110

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00523

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.0129

AC:

18812

AN:

1461674

Hom.:

149

Cov.:

AF XY:

0.0125

AC XY:

9106

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00458

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00822

AC:

1251

AN:

152278

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

588

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00303

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00793

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

DANN

Benign

0.60

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