4-89113573-C-T

Variant summary

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

The NM_145715.3(TIGD2):​c.599C>T​(p.Ser200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S200P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TIGD2
NM_145715.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45
Variant links:
Genes affected
TIGD2 (HGNC:18333): (tigger transposable element derived 2) 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]

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=0.13377166).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIGD2NM_145715.3 linkc.599C>T p.Ser200Phe missense_variant Exon 2 of 2 ENST00000603357.3 NP_663761.1 Q4W5G0V9HWD1B3KNK0
TIGD2NM_001382380.1 linkc.599C>T p.Ser200Phe missense_variant Exon 2 of 2 NP_001369309.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TIGD2ENST00000603357.3 linkc.599C>T p.Ser200Phe missense_variant Exon 2 of 2 4 NM_145715.3 ENSP00000486687.1 Q4W5G0

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251162
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461856
Hom.:
0
Cov.:
33
AF XY:
0.00000963
AC XY:
7
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.599C>T (p.S200F) alteration is located in exon 1 (coding exon 1) of the TIGD2 gene. This alteration results from a C to T substitution at nucleotide position 599, causing the serine (S) at amino acid position 200 to be replaced by a phenylalanine (F). 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
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.086
Sift
Uncertain
0.0040
.;D
Sift4G
Uncertain
0.018
D;D
Polyphen
0.0
B;B
Vest4
0.14
MutPred
0.51
Loss of disorder (P = 0.0112);Loss of disorder (P = 0.0112);
MVP
0.27
MPC
0.13
ClinPred
0.14
T
GERP RS
3.0
Varity_R
0.15
gMVP
0.20

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: rs780959909; hg19: chr4-90034724; API