chr11-65356847-G-A

Position:

• chr11-65356847-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_145719.3(TIGD3):​c.1039G>A​(p.Ala347Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TIGD3 NM_145719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

Genes affected

TIGD3 (HGNC:18334): (tigger transposable element derived 3) 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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.961

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGD3	NM_145719.3	c.1039G>A	p.Ala347Thr	missense_variant	2/2	ENST00000309880.6	NP_663771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGD3	ENST00000309880.6	c.1039G>A	p.Ala347Thr	missense_variant	2/2	2	NM_145719.3	ENSP00000308354.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 11, 2023

The c.1039G>A (p.A347T) alteration is located in exon 2 (coding exon 1) of the TIGD3 gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the alanine (A) at amino acid position 347 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.032	D
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	0.79	D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.49
Sift	Benign	0.26	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.86		Loss of catalytic residue at A347 (P = 0.1083);
MVP		0.77
MPC		1.2
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.094
gMVP		0.48

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: chr11-65124318; COSMIC: COSV52891650; COSMIC: COSV52891650;