8-143598012-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032862.5(TIGD5):​c.109C>T​(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,284,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TIGD5
NM_032862.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.487
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]
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]

Genome browser will be placed here

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=0.09414485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TIGD5NM_032862.5 linkuse as main transcriptc.109C>T p.Pro37Ser missense_variant 1/1 ENST00000504548.4 NP_116251.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TIGD5ENST00000504548.4 linkuse as main transcriptc.109C>T p.Pro37Ser missense_variant 1/1 NM_032862.5 ENSP00000421489 P1Q53EQ6-1
EEF1DENST00000533749.5 linkuse as main transcriptc.41+1269G>A intron_variant 5 ENSP00000431933

Frequencies

GnomAD3 genomes
AF:
0.0000607
AC:
9
AN:
148272
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000134
Gnomad ASJ
AF:
0.000875
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000300
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000238
AC:
27
AN:
1136116
Hom.:
0
Cov.:
30
AF XY:
0.0000311
AC XY:
17
AN XY:
547100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000132
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000342
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000316
Gnomad4 OTH exome
AF:
0.000110
GnomAD4 genome
AF:
0.0000607
AC:
9
AN:
148272
Hom.:
0
Cov.:
32
AF XY:
0.0000968
AC XY:
7
AN XY:
72332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000134
Gnomad4 ASJ
AF:
0.000875
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000300
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000416

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 submitterclinical testingAmbry GeneticsDec 01, 2022The c.109C>T (p.P37S) alteration is located in exon 1 (coding exon 1) of the TIGD5 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the proline (P) at amino acid position 37 to be replaced by a serine (S). 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
0.097
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.3
DANN
Benign
0.96
DEOGEN2
Benign
0.0066
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.12
N
REVEL
Benign
0.016
Sift
Benign
0.075
T
Sift4G
Pathogenic
0.0
D
Vest4
0.20
MutPred
0.31
Gain of phosphorylation at P37 (P = 9e-04);
MVP
0.18
MPC
0.83
ClinPred
0.058
T
GERP RS
-0.093
Varity_R
0.036
gMVP
0.36

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

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

Other links and lift over

dbSNP: rs941328379; hg19: chr8-144680182; API