Genetic Variant TIGD7:p.Val480Leu (chr16-3299177-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033208.4(TIGD7):c.1438G>C(p.Val480Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,587,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

TIGD7
NM_033208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.113

Publications

0 publications found

Variant links:

Genes affected

TIGD7 (HGNC:18331): (tigger transposable element derived 7) 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]

TIGD7 links:

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF263 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05441925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD7	NM_033208.4	MANE Select	c.1438G>C	p.Val480Leu	missense	Exon 2 of 2	NP_149985.2
	ZNF263	NM_001411015.1		c.*46+21C>G		intron	N/A	NP_001397944.1	D3DUC1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIGD7	ENST00000396862.2	TSL:2 MANE Select	c.1438G>C	p.Val480Leu	missense	Exon 2 of 2	ENSP00000380071.1	Q6NT04-1
TIGD7	ENST00000903484.1		c.1438G>C	p.Val480Leu	missense	Exon 2 of 2	ENSP00000573543.1
TIGD7	ENST00000903485.1		c.1438G>C	p.Val480Leu	missense	Exon 2 of 2	ENSP00000573544.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000660

AC:

AN:

227430

AF XY:

0.000114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000689

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000852

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.0000634

AC:

AN:

1435426

Hom.:

Cov.:

AF XY:

0.0000617

AC XY:

AN XY:

713438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32154

American (AMR)

AF:

0.0000508

AC:

AN:

39398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24906

East Asian (EAS)

AF:

0.00

AC:

AN:

38852

South Asian (SAS)

AF:

0.0000619

AC:

AN:

80820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52824

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000690

AC:

AN:

1101668

Other (OTH)

AF:

0.0000338

AC:

AN:

59154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.034

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.56

M_CAP

Benign

0.0027

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.11

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.89

REVEL

Benign

0.056

Sift

Uncertain

0.027

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.13

MutPred

0.21

Loss of methylation at K476 (P = 0.1002)

MVP

0.030

MPC

0.064

ClinPred

0.0063

GERP RS

0.55

Varity_R

0.069

gMVP

0.26

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over