Variant 8-23028346-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003842.5(TNFRSF10B):c.733A>C(p.Lys245Gln) 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 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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

TNFRSF10B
NM_003842.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.309

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1289838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNFRSF10B	NM_003842.5 linkuse as main transcript	c.733A>C	p.Lys245Gln	missense_variant	5/9	ENST00000276431.9
TNFRSF10B	NM_147187.3 linkuse as main transcript	c.646A>C	p.Lys216Gln	missense_variant	6/10
TNFRSF10B	NR_027140.2 linkuse as main transcript	n.677A>C		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10B	ENST00000276431.9 linkuse as main transcript	c.733A>C	p.Lys245Gln	missense_variant	5/9	1	NM_003842.5	P2	O14763-1
TNFRSF10B	ENST00000347739.3 linkuse as main transcript	c.646A>C	p.Lys216Gln	missense_variant	6/10	1		A2	O14763-2
TNFRSF10B	ENST00000518531.5 linkuse as main transcript	n.483A>C		non_coding_transcript_exon_variant	3/3	3
TNFRSF10B	ENST00000523504.5 linkuse as main transcript	c.*267A>C		3_prime_UTR_variant, NMD_transcript_variant	5/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 15, 2024

The c.646A>C (p.K216Q) alteration is located in exon 6 (coding exon 6) of the TNFRSF10B gene. This alteration results from a A to C substitution at nucleotide position 646, causing the lysine (K) at amino acid position 216 to be replaced by a glutamine (Q). 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

Benign

0.16

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

4.5

DANN

Benign

0.27

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.072

Sift

Benign

0.20

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.68

P;P

Vest4

0.065

MutPred

0.51

Loss of methylation at K245 (P = 0.0014);.;

MVP

0.91

MPC

0.23

ClinPred

0.11

GERP RS

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.076

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over