4-89113339-C-G

Variant names:

• chr4-89113339-C-G
• NM_145715.3:c.365C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_145715.3(TIGD2):​c.365C>G​(p.Ser122Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: TIGD2 NM_145715.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGD2	NM_145715.3	c.365C>G	p.Ser122Trp	missense_variant	Exon 2 of 2	ENST00000603357.3	NP_663761.1
TIGD2	NM_001382380.1	c.365C>G	p.Ser122Trp	missense_variant	Exon 2 of 2		NP_001369309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGD2	ENST00000603357.3	c.365C>G	p.Ser122Trp	missense_variant	Exon 2 of 2	4	NM_145715.3	ENSP00000486687.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.365C>G (p.S122W) alteration is located in exon 1 (coding exon 1) of the TIGD2 gene. This alteration results from a C to G substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by a tryptophan (W). 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	0.98
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D;D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.93	.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.8	H;H
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.3	.;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.68
MutPred		0.88		Gain of MoRF binding (P = 0.0321);Gain of MoRF binding (P = 0.0321);
MVP		0.57
MPC		0.66
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.74
gMVP		0.75
Mutation Taster		=72/28	polymorphism

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: chr4-90034490;