chr4-152770188-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145720.4(TIGD4):​c.817G>A​(p.Asp273Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TIGD4
NM_145720.4 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54
Variant links:
Genes affected
TIGD4 (HGNC:18335): (tigger transposable element derived 4) 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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIGD4NM_145720.4 linkc.817G>A p.Asp273Asn missense_variant Exon 2 of 2 ENST00000304337.3 NP_663772.1 Q8IY51
TIGD4XM_005262807.5 linkc.817G>A p.Asp273Asn missense_variant Exon 3 of 3 XP_005262864.1 Q8IY51

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TIGD4ENST00000304337.3 linkc.817G>A p.Asp273Asn missense_variant Exon 2 of 2 1 NM_145720.4 ENSP00000355162.2 Q8IY51

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251282
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461786
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727190
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.817G>A (p.D273N) alteration is located in exon 2 (coding exon 1) of the TIGD4 gene. This alteration results from a G to A substitution at nucleotide position 817, causing the aspartic acid (D) at amino acid position 273 to be replaced by an asparagine (N). 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
0.34
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.067
T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.012
T
MetaRNN
Pathogenic
0.78
D
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.71
MutPred
0.59
Gain of MoRF binding (P = 0.0399);
MVP
0.55
MPC
0.17
ClinPred
0.97
D
GERP RS
6.0
Varity_R
0.76
gMVP
0.52

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: rs768876332; hg19: chr4-153691340; API