16-67154771-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003789.4(TRADD):c.817G>A(p.Val273Met) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,604,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
TRADD
NM_003789.4 missense
NM_003789.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.07
Genes affected
TRADD (HGNC:12030): (TNFRSF1A associated via death domain) The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11050516).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRADD | NM_003789.4 | c.817G>A | p.Val273Met | missense_variant | 5/5 | ENST00000345057.9 | |
TRADD | NM_001323552.2 | c.817G>A | p.Val273Met | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRADD | ENST00000345057.9 | c.817G>A | p.Val273Met | missense_variant | 5/5 | 1 | NM_003789.4 | P1 | |
TRADD | ENST00000486556.1 | c.637G>A | p.Val213Met | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000540 AC: 12AN: 222232Hom.: 0 AF XY: 0.0000816 AC XY: 10AN XY: 122492
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GnomAD4 exome AF: 0.000116 AC: 168AN: 1452156Hom.: 1 Cov.: 31 AF XY: 0.000133 AC XY: 96AN XY: 721856
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74366
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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 | Dec 21, 2022 | The c.817G>A (p.V273M) alteration is located in exon 5 (coding exon 4) of the TRADD gene. This alteration results from a G to A substitution at nucleotide position 817, causing the valine (V) at amino acid position 273 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at