chr16-67155615-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003789.4(TRADD):c.191T>C(p.Ile64Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TRADD
NM_003789.4 missense
NM_003789.4 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 7.15
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRADD | NM_003789.4 | c.191T>C | p.Ile64Thr | missense_variant | 3/5 | ENST00000345057.9 | |
TRADD | NM_001323552.2 | c.191T>C | p.Ile64Thr | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRADD | ENST00000345057.9 | c.191T>C | p.Ile64Thr | missense_variant | 3/5 | 1 | NM_003789.4 | P1 | |
TRADD | ENST00000486556.1 | c.11T>C | p.Ile4Thr | missense_variant | 1/3 | 2 | |||
TRADD | ENST00000563348.1 | n.757T>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.12e-7 AC: 1AN: 1405100Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1AN XY: 695344
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74286
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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 | Sep 22, 2023 | The c.191T>C (p.I64T) alteration is located in exon 3 (coding exon 2) of the TRADD gene. This alteration results from a T to C substitution at nucleotide position 191, causing the isoleucine (I) at amino acid position 64 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Benign
D;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of stability (P = 0.0151);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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