chr5-149995130-T-C

Variant names:

• chr5-149995130-T-C
• rs144692725
• NM_030953.4:c.1219A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030953.4(TIGD6):​c.1219A>G​(p.Ile407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,614,272 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000070 (2 hom.)
• Consequence: TIGD6 NM_030953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.289
• Publications: 0 publications found

Genes affected

TIGD6 (HGNC:18332): (tigger transposable element derived 6) 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. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052191615).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030953.4. 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
	TIGD6	NM_030953.4	MANE Select	c.1219A>G	p.Ile407Val	missense	Exon 2 of 2	NP_112215.1	Q17RP2
	TIGD6	NM_001243253.2		c.1219A>G	p.Ile407Val	missense	Exon 2 of 2	NP_001230182.1	Q17RP2
	TIGD6	NM_001412172.1		c.1219A>G	p.Ile407Val	missense	Exon 3 of 3	NP_001399101.1	Q17RP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD6	ENST00000296736.4	TSL:1 MANE Select	c.1219A>G	p.Ile407Val	missense	Exon 2 of 2	ENSP00000296736.3	Q17RP2
	TIGD6	ENST00000515406.2	TSL:1	c.1219A>G	p.Ile407Val	missense	Exon 2 of 2	ENSP00000425318.2	Q17RP2
	TIGD6	ENST00000893998.1		c.1219A>G	p.Ile407Val	missense	Exon 3 of 3	ENSP00000564057.1

Frequencies

GnomAD3 genomes AF: 0.000420 AC: 64 AN: 152262 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 32 AN: 251418 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000698 AC: 102 AN: 1461892 Hom.: 2 Cov.: 30 AF XY: 0.0000701 AC XY: 51 AN XY: 727248

African (AFR) AF: 0.00131 AC: 44 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1112012

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152380 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74518

African (AFR) AF: 0.00142 AC: 59 AN: 41586

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000225 Hom.: 1

Bravo AF: 0.000586

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	0.066
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.83
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.29
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.078
Sift	Benign	0.29	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.066
MVP		0.16
MPC		0.026
ClinPred		0.0037	T
GERP RS		-3.5
Varity_R		0.029
gMVP		0.059
Mutation Taster		=97/3	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: rs144692725; hg19: chr5-149374693;