Variant 8-23114662-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000520607(ENSG00000284956):c.-70C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

ENSG00000284956
ENST00000520607 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.319

Variant links:

Genes affected

ENSG00000284956 (HGNC:):

ENSG00000284956 links:

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022176743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5 linkuse as main transcript	c.172C>G	p.His58Asp	missense_variant	3/5	ENST00000356864.4	NP_003832.3	O14798

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENSG00000284956	ENST00000520607 linkuse as main transcript	c.-70C>G		5_prime_UTR_premature_start_codon_gain_variant	5/6	4		ENSP00000493787.1	A0A2R8YDH7
TNFRSF10C	ENST00000356864.4 linkuse as main transcript	c.172C>G	p.His58Asp	missense_variant	3/5	1	NM_003841.5	ENSP00000349324.4	O14798
ENSG00000284956	ENST00000520607 linkuse as main transcript	c.-70C>G		5_prime_UTR_variant	5/6	4		ENSP00000493787.1	A0A2R8YDH7

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251218

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000493

AC:

AN:

1460944

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000519

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000791

Hom.:

Bravo

AF:

0.000597

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.172C>G (p.H58D) alteration is located in exon 3 (coding exon 3) of the TNFRSF10C gene. This alteration results from a C to G substitution at nucleotide position 172, causing the histidine (H) at amino acid position 58 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.26

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.57

M_CAP

Benign

0.0065

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.052

Sift

Uncertain

0.0030

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.42

MVP

0.44

MPC

0.038

ClinPred

0.14

GERP RS

-2.6

Varity_R

0.17

gMVP

0.79

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