4-152769744-C-T

Variant summary

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

The NM_145720.4(TIGD4):​c.1261G>A​(p.Ala421Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TIGD4
NM_145720.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIGD4NM_145720.4 linkc.1261G>A p.Ala421Thr missense_variant Exon 2 of 2 ENST00000304337.3 NP_663772.1 Q8IY51
TIGD4XM_005262807.5 linkc.1261G>A p.Ala421Thr 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.1261G>A p.Ala421Thr missense_variant Exon 2 of 2 1 NM_145720.4 ENSP00000355162.2 Q8IY51

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1261G>A (p.A421T) 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 1261, causing the alanine (A) at amino acid position 421 to be replaced by a threonine (T). 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
0.17
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0036
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0044
T
MetaRNN
Uncertain
0.48
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.78
N
REVEL
Benign
0.18
Sift
Benign
0.16
T
Sift4G
Uncertain
0.047
D
Polyphen
0.96
P
Vest4
0.63
MutPred
0.43
Gain of glycosylation at Y420 (P = 0.0044);
MVP
0.17
MPC
0.16
ClinPred
0.73
D
GERP RS
6.2
Varity_R
0.085
gMVP
0.15

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.

Other links and lift over

hg19: chr4-153690896; API