5-149995100-A-G

Variant names:

• chr5-149995100-A-G
• rs1755350646
• NM_030953.4:c.1249T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030953.4(TIGD6):​c.1249T>C​(p.Phe417Leu) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TIGD6 NM_030953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.656

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12018892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGD6	NM_030953.4	c.1249T>C	p.Phe417Leu	missense_variant	Exon 2 of 2	ENST00000296736.4	NP_112215.1
TIGD6	NM_001243253.2	c.1249T>C	p.Phe417Leu	missense_variant	Exon 2 of 2		NP_001230182.1
TIGD6	NM_001412172.1	c.1249T>C	p.Phe417Leu	missense_variant	Exon 3 of 3		NP_001399101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGD6	ENST00000296736.4	c.1249T>C	p.Phe417Leu	missense_variant	Exon 2 of 2	1	NM_030953.4	ENSP00000296736.3
TIGD6	ENST00000515406.2	c.1249T>C	p.Phe417Leu	missense_variant	Exon 2 of 2	1		ENSP00000425318.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1249T>C (p.F417L) alteration is located in exon 2 (coding exon 1) of the TIGD6 gene. This alteration results from a T to C substitution at nucleotide position 1249, causing the phenylalanine (F) at amino acid position 417 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.034
Sift	Benign	0.64	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.14	B;B
Vest4		0.27
MutPred		0.69		Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);
MVP		0.20
MPC		0.032
ClinPred		0.070	T
GERP RS		2.8
Varity_R		0.066
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs1755350646; hg19: chr5-149374663;