chr8-143598685-C-A

Position:

• chr8-143598685-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032862.5(TIGD5):​c.782C>A​(p.Pro261His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIGD5 NM_032862.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118

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]

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]

ACMG classification

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=0.09479642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGD5	NM_032862.5	c.782C>A	p.Pro261His	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	c.782C>A	p.Pro261His	missense_variant	1/1	6	NM_032862.5	ENSP00000421489.2
EEF1D	ENST00000533749.5	c.41+596G>T		intron_variant		5		ENSP00000431933.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1349340 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 665990

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.782C>A (p.P261H) alteration is located in exon 1 (coding exon 1) of the TIGD5 gene. This alteration results from a C to A substitution at nucleotide position 782, causing the proline (P) at amino acid position 261 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.024
Sift	Benign	0.073	T
Sift4G	Uncertain	0.0040	D
Vest4		0.13
MVP		0.44
MPC		1.5
ClinPred		0.23	T
GERP RS		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs1449782639; hg19: chr8-144680855;