Variant 16-67155634-C-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_003789.4(TRADD):c.172G>C(p.Val58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.0000021 ( 0 hom. )

Consequence

TRADD
NM_003789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Variant links:

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]

TRADD 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=0.14113417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRADD	NM_003789.4 linkuse as main transcript	c.172G>C	p.Val58Leu	missense_variant	3/5	ENST00000345057.9
TRADD	NM_001323552.2 linkuse as main transcript	c.172G>C	p.Val58Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRADD	ENST00000345057.9 linkuse as main transcript	c.172G>C	p.Val58Leu	missense_variant	3/5	1	NM_003789.4	P1	Q15628-1
TRADD	ENST00000486556.1 linkuse as main transcript	c.-9G>C		5_prime_UTR_variant	1/3	2			Q15628-2
TRADD	ENST00000563348.1 linkuse as main transcript	n.738G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

153652

Hom.:

AF XY:

0.0000117

AC XY:

AN XY:

85422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1401988

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000768

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:

0.00

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

Nov 18, 2022

The c.172G>C (p.V58L) alteration is located in exon 3 (coding exon 2) of the TRADD gene. This alteration results from a G to C substitution at nucleotide position 172, causing the valine (V) at amino acid position 58 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.71

M_CAP

Benign

0.0073

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.99

REVEL

Benign

0.043

Sift

Benign

0.24

Sift4G

Benign

0.11

Polyphen

0.012

Vest4

0.11

MutPred

0.72

Loss of methylation at K63 (P = 0.0847);

MVP

0.12

MPC

0.74

ClinPred

0.049

GERP RS

2.5

Varity_R

0.10

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over