Genetic Variant NM_003842.5:c.124G>A (chr8-23068771-C-T) – 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_003842.5(TNFRSF10B):c.124G>A(p.Val42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNFRSF10B
NM_003842.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

0 publications found

Variant links:

Genes affected

TNFRSF10B (HGNC:11905): (TNF receptor superfamily member 10b) The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]

TNFRSF10B Gene-Disease associations (from GenCC):

head and neck squamous cell carcinoma
Inheritance: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

TNFRSF10B links:

TNFRSF10B-AS1 (HGNC:27809):

TNFRSF10B-AS1 links:

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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=0.11199978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003842.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF10B	NM_003842.5	MANE Select	c.124G>A	p.Val42Ile	missense	Exon 1 of 9	NP_003833.4
TNFRSF10B	NM_147187.3		c.124G>A	p.Val42Ile	missense	Exon 1 of 10	NP_671716.2	O14763-2
TNFRSF10B	NR_027140.2		n.261G>A		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.124G>A	p.Val42Ile	missense	Exon 1 of 9	ENSP00000276431.4	O14763-1
TNFRSF10B	ENST00000347739.3	TSL:1	c.124G>A	p.Val42Ile	missense	Exon 1 of 10	ENSP00000317859.3	O14763-2
TNFRSF10B	ENST00000931215.1		c.124G>A	p.Val42Ile	missense	Exon 1 of 9	ENSP00000601274.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718390

African (AFR)

AF:

0.00

AC:

AN:

33184

American (AMR)

AF:

0.00

AC:

AN:

42590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

39142

South Asian (SAS)

AF:

0.00

AC:

AN:

84746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104682

Other (OTH)

AF:

0.00

AC:

AN:

59714

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

0.11

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.7

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.059

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.41

M_CAP

Benign

0.037

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.0

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.18

REVEL

Benign

0.23

Sift

Benign

0.78

Sift4G

Benign

0.18

Polyphen

0.54

Vest4

0.18

MutPred

0.36

Loss of catalytic residue at V42 (P = 0.005)

MVP

0.66

MPC

0.14

ClinPred

0.21

GERP RS

1.6

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.021

gMVP

0.17

Mutation Taster

=88/12

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over