Variant 12-112141016-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006700.3(TRAFD1):c.435G>C(p.Glu145Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,192 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TRAFD1
NM_006700.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.206

Variant links:

Genes affected

TRAFD1 (HGNC:24808): (TRAF-type zinc finger domain containing 1) The innate immune system confers host defense against viral and microbial infection, and TRAFD1 is a negative feedback regulator that controls excessive immune responses (Sanada et al., 2008 [PubMed 18849341]).[supplied by OMIM, Dec 2009]

TRAFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02246043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAFD1	NM_006700.3 link	c.435G>C	p.Glu145Asp	missense_variant	5/12	ENST00000412615.7	NP_006691.1	O14545-1A0A024RBK4
TRAFD1	NM_001143906.2 link	c.435G>C	p.Glu145Asp	missense_variant	5/12		NP_001137378.1	O14545-1A0A024RBK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAFD1	ENST00000412615.7 link	c.435G>C	p.Glu145Asp	missense_variant	5/12	1	NM_006700.3	ENSP00000396526.2		O14545-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251464

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

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:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Aug 09, 2021

The c.435G>C (p.E145D) alteration is located in exon 5 (coding exon 4) of the TRAFD1 gene. This alteration results from a G to C substitution at nucleotide position 435, causing the glutamic acid (E) at amino acid position 145 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.24

B;B;B

Vest4

0.063

MutPred

0.29

Loss of methylation at K142 (P = 0.095);Loss of methylation at K142 (P = 0.095);Loss of methylation at K142 (P = 0.095);

MVP

0.17

MPC

0.10

ClinPred

0.013

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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