8-23103164-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003841.5(TNFRSF10C):c.43G>T(p.Val15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,611,782 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

TNFRSF10C
NM_003841.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.681

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004609883).

BP6

Variant 8-23103164-G-T is Benign according to our data. Variant chr8-23103164-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 732374.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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.43G>T	p.Val15Phe	missense	Exon 1 of 5	NP_003832.3
	LOC254896	NR_046173.1		n.848G>T		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.43G>T	p.Val15Phe	missense	Exon 1 of 5	ENSP00000349324.4	O14798
ENSG00000284956	ENST00000520607.1	TSL:4	c.-182+2480G>T		intron	N/A	ENSP00000493787.1	A0A2R8YDH7
TNFRSF10C	ENST00000877636.1		c.43G>T	p.Val15Phe	missense	Exon 1 of 6	ENSP00000547695.1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

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:

0.000479

GnomAD2 exomes

AF:

0.000439

AC:

106

AN:

241416

AF XY:

0.000305

show subpopulations

Gnomad AFR exome

AF:

0.00578

Gnomad AMR exome

AF:

0.000441

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000216

AC:

315

AN:

1459468

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

725842

show subpopulations

African (AFR)

AF:

0.00732

AC:

245

AN:

33448

American (AMR)

AF:

0.000585

AC:

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111194

Other (OTH)

AF:

0.000630

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

107

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

AF:

0.00183

AC:

279

AN:

152314

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00654

AC:

272

AN:

41576

American (AMR)

AF:

0.000392

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000768

Hom.:

Bravo

AF:

0.00222

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000536

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.97

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.42

M_CAP

Benign

0.010

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

PhyloP100

-0.68

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.66

REVEL

Benign

0.13

Sift

Benign

0.054

Sift4G

Uncertain

0.0060

Polyphen

0.88

Vest4

0.15

MVP

0.47

MPC

0.0082

ClinPred

0.017

GERP RS

-1.8

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.099

gMVP

0.55

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over