rs943892942

Variant names:

• chr4-152769590-T-C
• rs943892942
• NM_145720.4:c.1415A>G

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.1415A>G​(p.Lys472Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,434 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: TIGD4 NM_145720.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• 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=0.07738215).

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.1415A>G	p.Lys472Arg	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.1415A>G	p.Lys472Arg	missense	Exon 2 of 2	ENSP00000355162.2	Q8IY51
	TIGD4	ENST00000891947.1		c.1415A>G	p.Lys472Arg	missense	Exon 3 of 3	ENSP00000562006.1
	TIGD4	ENST00000914394.1		c.1415A>G	p.Lys472Arg	missense	Exon 2 of 2	ENSP00000584453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461434 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726978

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000929 AC: 8 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111794

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.011
Sift	Benign	0.78	T
Sift4G	Benign	0.82	T
Polyphen		0.22	B
Vest4		0.36
MutPred		0.23		Loss of ubiquitination at K472 (P = 0.0034)
MVP		0.067
MPC		0.022
ClinPred		0.15	T
GERP RS		3.6
Varity_R		0.041
gMVP		0.20
Mutation Taster		=100/0	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: rs943892942; hg19: chr4-153690742;