chr16-30088717-GGA-ACT

Variant names:

• chr16-30088717-GGA-ACT
• NM_004608.4:c.742_744delTCCinsAGT
• TBX6 p.249

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004608.4(TBX6):​c.742_744delTCCinsAGT​(p.249) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S248S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBX6 NM_004608.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94
• Publications: 0 publications found

Genes affected

TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

TBX6 Gene-Disease associations (from GenCC):

• Mayer-Rokitansky-Kuster-Hauser syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• spondylocostal dysostosis 5

  Inheritance: Unknown, SD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• autosomal dominant spondylocostal dysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004608.4. 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
	TBX6	NM_004608.4	MANE Select	c.742_744delTCCinsAGT	p.249	synonymous	N/A	NP_004599.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	ENST00000395224.7	TSL:1 MANE Select	c.742_744delTCCinsAGT	p.249	synonymous	N/A	ENSP00000378650.2	O95947-1
	TBX6	ENST00000279386.6	TSL:1	c.742_744delTCCinsAGT	p.249	synonymous	N/A	ENSP00000279386.2	O95947-1
	TBX6	ENST00000553607.1	TSL:1	c.742_744delTCCinsAGT	p.249	synonymous	N/A	ENSP00000461223.1	O95947-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-30100038;