4-152769782-C-T

Variant names:

• chr4-152769782-C-T
• rs756454733
• NM_145720.4:c.1223G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145720.4(TIGD4):​c.1223G>A​(p.Gly408Glu) 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 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G408A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TIGD4 NM_145720.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

TIGD4 (HGNC:18335): (tigger transposable element derived 4) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089496225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145720.4. 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
	TIGD4	NM_145720.4	MANE Select	c.1223G>A	p.Gly408Glu	missense	Exon 2 of 2	NP_663772.1	Q8IY51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD4	ENST00000304337.3	TSL:1 MANE Select	c.1223G>A	p.Gly408Glu	missense	Exon 2 of 2	ENSP00000355162.2	Q8IY51
	TIGD4	ENST00000891947.1		c.1223G>A	p.Gly408Glu	missense	Exon 3 of 3	ENSP00000562006.1
	TIGD4	ENST00000914394.1		c.1223G>A	p.Gly408Glu	missense	Exon 2 of 2	ENSP00000584453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250912 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461240 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726946

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111938

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.046
Sift	Benign	0.42	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.48		Loss of helix (P = 0.0626)
MVP		0.24
MPC		0.022
ClinPred		0.067	T
GERP RS		3.5
Varity_R		0.052
gMVP		0.32
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs756454733; hg19: chr4-153690934;