Genetic Variant TIGD7:p.Ser540Thr (chr16-3298996-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033208.4(TIGD7):c.1619G>C(p.Ser540Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000855 in 1,169,912 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S540G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

TIGD7
NM_033208.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.836

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03172049).

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.1619G>C	p.Ser540Thr	missense	Exon 2 of 2	NP_149985.2
	ZNF263	NM_001411015.1		c.2048-110C>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.1619G>C	p.Ser540Thr	missense	Exon 2 of 2	ENSP00000380071.1	Q6NT04-1
TIGD7	ENST00000903484.1		c.1619G>C	p.Ser540Thr	missense	Exon 2 of 2	ENSP00000573543.1
TIGD7	ENST00000903485.1		c.1619G>C	p.Ser540Thr	missense	Exon 2 of 2	ENSP00000573544.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.55e-7

AC:

AN:

1169912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

561800

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24802

American (AMR)

AF:

0.00

AC:

AN:

18078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15670

East Asian (EAS)

AF:

0.00

AC:

AN:

30830

South Asian (SAS)

AF:

0.00

AC:

AN:

30810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4670

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

955346

Other (OTH)

AF:

0.00

AC:

AN:

47156

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.90

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.015

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.39

M_CAP

Benign

0.0048

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.84

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.18

REVEL

Benign

0.057

Sift

Benign

0.051

Sift4G

Benign

0.11

Polyphen

0.018

Vest4

0.11

MutPred

0.063

Loss of glycosylation at S540 (P = 0.0242)

MVP

0.014

MPC

0.060

ClinPred

0.11

GERP RS

-0.53

Varity_R

0.056

gMVP

0.066

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over