chr4-152769744-C-T

Variant names:

• chr4-152769744-C-T
• NM_145720.4:c.1261G>A

Variant summary

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

The NM_145720.4(TIGD4):​c.1261G>A​(p.Ala421Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIGD4 NM_145720.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1261G>A	p.Ala421Thr	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.1261G>A	p.Ala421Thr	missense	Exon 2 of 2	ENSP00000355162.2	Q8IY51
	TIGD4	ENST00000891947.1		c.1261G>A	p.Ala421Thr	missense	Exon 3 of 3	ENSP00000562006.1
	TIGD4	ENST00000914394.1		c.1261G>A	p.Ala421Thr	missense	Exon 2 of 2	ENSP00000584453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	0.17
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.18
Sift	Benign	0.16	T
Sift4G	Uncertain	0.047	D
Polyphen		0.96	P
Vest4		0.63
MutPred		0.43		Gain of glycosylation at Y420 (P = 0.0044)
MVP		0.17
MPC		0.16
ClinPred		0.73	D
GERP RS		6.2
Varity_R		0.085
gMVP		0.15
Mutation Taster		=93/7	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

hg19: chr4-153690896;