4-152770067-G-T

Variant names:

• chr4-152770067-G-T
• rs1330636266
• NM_145720.4:c.938C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145720.4(TIGD4):​c.938C>A​(p.Ser313Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TIGD4 NM_145720.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGD4	NM_145720.4	c.938C>A	p.Ser313Tyr	missense_variant	Exon 2 of 2	ENST00000304337.3	NP_663772.1
TIGD4	XM_005262807.5	c.938C>A	p.Ser313Tyr	missense_variant	Exon 3 of 3		XP_005262864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGD4	ENST00000304337.3	c.938C>A	p.Ser313Tyr	missense_variant	Exon 2 of 2	1	NM_145720.4	ENSP00000355162.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461660 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727108

Gnomad4 AFR exome AF: 0.0000896

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.938C>A (p.S313Y) alteration is located in exon 2 (coding exon 1) of the TIGD4 gene. This alteration results from a C to A substitution at nucleotide position 938, causing the serine (S) at amino acid position 313 to be replaced by a tyrosine (Y). 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	Benign	0.13
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.035	D
Polyphen		0.98	D
Vest4		0.59
MutPred		0.69		Gain of catalytic residue at S313 (P = 0.0026);
MVP		0.59
MPC		0.16
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.86
gMVP		0.52

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: rs1330636266; hg19: chr4-153691219;