Variant 4-89113572-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145715.3(TIGD2):c.598T>C(p.Ser200Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TIGD2
NM_145715.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

Variant links:

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]

TIGD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032805294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGD2	NM_145715.3 linkuse as main transcript	c.598T>C	p.Ser200Pro	missense_variant	2/2	ENST00000603357.3	NP_663761.1
TIGD2	NM_001382380.1 linkuse as main transcript	c.598T>C	p.Ser200Pro	missense_variant	2/2		NP_001369309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGD2	ENST00000603357.3 linkuse as main transcript	c.598T>C	p.Ser200Pro	missense_variant	2/2	4	NM_145715.3	ENSP00000486687	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.598T>C (p.S200P) 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 598, causing the serine (S) at amino acid position 200 to be replaced by a proline (P). 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

0.075

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.23

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

2.6

.;N

REVEL

Benign

0.050

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.088

MutPred

0.49

Loss of glycosylation at S200 (P = 0.0322);Loss of glycosylation at S200 (P = 0.0322);

MVP

0.061

MPC

0.15

ClinPred

0.036

GERP RS

-0.19

Varity_R

0.16

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over