16-30086868-GTGATGA-GTGATGATGA

Variant names:

• chr16-30086868-G-GTGA
• rs3833842
• NM_004608.4:c.840-20_840-18dupTCA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004608.4(TBX6):​c.840-20_840-18dupTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: TBX6 NM_004608.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.547
• Publications: 4 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):

• spondylocostal dysostosis 5

  Inheritance: Unknown, SD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 16-30086868-G-GTGA is Benign according to our data. Variant chr16-30086868-G-GTGA is described in ClinVar as Likely_benign. ClinVar VariationId is 1985529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 Unknown,AD,SD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	NM_004608.4	MANE Select	c.840-20_840-18dupTCA		intron	N/A	NP_004599.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	ENST00000395224.7	TSL:1 MANE Select	c.840-18_840-17insTCA		intron	N/A	ENSP00000378650.2
	TBX6	ENST00000279386.6	TSL:1	c.840-18_840-17insTCA		intron	N/A	ENSP00000279386.2
	TBX6	ENST00000567664.5	TSL:5	n.*48-174_*48-173insTCA		intron	N/A	ENSP00000460425.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151724 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000900 AC: 20 AN: 222238 AF XY: 0.0000833

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000627

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000318 AC: 46 AN: 1448364 Hom.: 0 Cov.: 0 AF XY: 0.0000264 AC XY: 19 AN XY: 719694

African (AFR) AF: 0.0000300 AC: 1 AN: 33340

American (AMR) AF: 0.0000689 AC: 3 AN: 43532

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25928

East Asian (EAS) AF: 0.000330 AC: 13 AN: 39360

South Asian (SAS) AF: 0.0000355 AC: 3 AN: 84574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000217 AC: 24 AN: 1105946

Other (OTH) AF: 0.0000167 AC: 1 AN: 59878

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151842 Hom.: 0 Cov.: 0 AF XY: 0.0000539 AC XY: 4 AN XY: 74196

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.000131 AC: 2 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 1171

Bravo AF: 0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3833842; hg19: chr16-30098189;