4-89113758-T-C

Position:

• chr4-89113758-T-C

Variant summary

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

The NM_145715.3(TIGD2):​c.784T>C​(p.Phe262Leu) 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: 33)
• Consequence: TIGD2 NM_145715.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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]

ACMG classification

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/exons	MANE	Protein	UniProt
TIGD2	NM_145715.3	c.784T>C	p.Phe262Leu	missense_variant	2/2	ENST00000603357.3	NP_663761.1
TIGD2	NM_001382380.1	c.784T>C	p.Phe262Leu	missense_variant	2/2		NP_001369309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGD2	ENST00000603357.3	c.784T>C	p.Phe262Leu	missense_variant	2/2	4	NM_145715.3	ENSP00000486687.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Mar 30, 2024

The c.784T>C (p.F262L) alteration is located in exon 1 (coding exon 1) of the TIGD2 gene. This alteration results from a T to C substitution at nucleotide position 784, causing the phenylalanine (F) at amino acid position 262 to be replaced by a leucine (L). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.9	.;D
REVEL	Benign	0.17
Sift	Benign	0.097	.;T
Sift4G	Benign	0.11	T;T
Polyphen		0.0080	B;B
Vest4		0.50
MutPred		0.83		Loss of catalytic residue at R263 (P = 0.1094);Loss of catalytic residue at R263 (P = 0.1094);
MVP		0.38
MPC		0.16
ClinPred		0.89	D
GERP RS		3.3
Varity_R		0.27
gMVP		0.51

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: chr4-90034909;