Genetic Variant NM_003841.5:c.17A>C (chr8-23103138-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003841.5(TNFRSF10C):c.17A>C(p.Lys6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TNFRSF10C
NM_003841.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.919

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10929498).

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.17A>C	p.Lys6Thr	missense	Exon 1 of 5	NP_003832.3
	LOC254896	NR_046173.1		n.822A>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF10C	ENST00000356864.4	TSL:1 MANE Select	c.17A>C	p.Lys6Thr	missense	Exon 1 of 5	ENSP00000349324.4	O14798
ENSG00000284956	ENST00000520607.1	TSL:4	c.-182+2454A>C		intron	N/A	ENSP00000493787.1	A0A2R8YDH7
TNFRSF10C	ENST00000877636.1		c.17A>C	p.Lys6Thr	missense	Exon 1 of 6	ENSP00000547695.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460100

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111410

Other (OTH)

AF:

0.0000166

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.9

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.014

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.52

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

-0.92

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

REVEL

Benign

0.071

Sift

Uncertain

0.026

Sift4G

Uncertain

0.013

Polyphen

0.90

Vest4

0.12

MutPred

0.39

Loss of methylation at K6 (P = 0.0098)

MVP

0.59

MPC

0.021

ClinPred

0.50

GERP RS

-0.46

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.086

gMVP

0.53

Mutation Taster

=300/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over