Variant 8-143598586-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032862.5(TIGD5):c.683A>C(p.Glu228Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TIGD5
NM_032862.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

TIGD5 (HGNC:18336): (tigger transposable element derived 5) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

TIGD5 links:

EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

EEF1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17278698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGD5	NM_032862.5 linkuse as main transcript	c.683A>C	p.Glu228Ala	missense_variant	1/1	ENST00000504548.4	NP_116251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGD5	ENST00000504548.4 linkuse as main transcript	c.683A>C	p.Glu228Ala	missense_variant	1/1		NM_032862.5	ENSP00000421489	P1	Q53EQ6-1
EEF1D	ENST00000533749.5 linkuse as main transcript	c.41+695T>G		intron_variant		5		ENSP00000431933

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146088

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000230

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00211

AC:

2061

AN:

977374

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1022

AN XY:

476070

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.00951

Gnomad4 ASJ exome

AF:

0.00734

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.000323

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000137

AC:

AN:

146202

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71384

show subpopulations

Gnomad4 AFR

AF:

0.0000248

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000231

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 27, 2023

The c.683A>C (p.E228A) alteration is located in exon 1 (coding exon 1) of the TIGD5 gene. This alteration results from a A to C substitution at nucleotide position 683, causing the glutamic acid (E) at amino acid position 228 to be replaced by an alanine (A). 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

0.067

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.022

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.9

REVEL

Benign

0.092

Sift

Benign

0.21

Sift4G

Benign

0.66

Vest4

0.077

MVP

0.030

MPC

0.88

ClinPred

0.060

GERP RS

3.1

Varity_R

0.063

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over