NM_003842.5:c.1072A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003842.5(TNFRSF10B):​c.1072A>T​(p.Met358Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M358I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

TNFRSF10B
NM_003842.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.107
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26624864).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNFRSF10BNM_003842.5 linkc.1072A>T p.Met358Leu missense_variant Exon 9 of 9 ENST00000276431.9 NP_003833.4 O14763-1Q7Z2I8
TNFRSF10BNM_147187.3 linkc.985A>T p.Met329Leu missense_variant Exon 10 of 10 NP_671716.2 O14763-2
TNFRSF10BNR_027140.2 linkn.1016A>T non_coding_transcript_exon_variant Exon 9 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNFRSF10BENST00000276431.9 linkc.1072A>T p.Met358Leu missense_variant Exon 9 of 9 1 NM_003842.5 ENSP00000276431.4 O14763-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
6.2
DANN
Benign
0.56
DEOGEN2
Benign
0.38
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.57
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.26
Sift
Uncertain
0.022
D;D
Sift4G
Benign
0.074
T;T
Polyphen
0.038
B;P
Vest4
0.17
MutPred
0.57
Gain of helix (P = 0.0854);.;
MVP
0.69
MPC
0.059
ClinPred
0.11
T
GERP RS
-0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-22880435; API