6-166158401-T-TGGCCGC

Variant names:

• chr6-166158401-T-TGGCCGC
• NM_001366285.2:c.1219_1224dupGCGGCC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001366285.2(TBXT):​c.1219_1224dupGCGGCC​(p.Ala407_Ala408dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBXT NM_001366285.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.248

Genes affected

TBXT (HGNC:11515): (T-box transcription factor T) The protein encoded by this gene is an embryonic nuclear transcription factor that binds to a specific DNA element, the palindromic T-site. It binds through a region in its N-terminus, called the T-box, and effects transcription of genes required for mesoderm formation and differentiation. The protein is localized to notochord-derived cells. Variation in this gene was associated with susceptibility to neural tube defects and chordoma. A mutation in this gene was found in a family with sacral agenesis with vertebral anomalies. [provided by RefSeq, Sep 2018]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001366285.2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.1219_1224dupGCGGCC	p.Ala407_Ala408dup	conservative_inframe_insertion	Exon 8 of 8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.1219_1224dupGCGGCC	p.Ala407_Ala408dup	conservative_inframe_insertion	Exon 8 of 8	1	NM_001366285.2	ENSP00000355841.3
TBXT	ENST00000366871.7	c.1042_1047dupGCGGCC	p.Ala348_Ala349dup	conservative_inframe_insertion	Exon 8 of 8	1		ENSP00000355836.3
TBXT	ENST00000296946.6	c.1216_1221dupGCGGCC	p.Ala406_Ala407dup	conservative_inframe_insertion	Exon 9 of 9	5		ENSP00000296946.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TBXT: PM2, PM4:Supporting -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-166571889;