16-30086868-GTGATGA-GTGA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004608.4(TBX6):​c.840-20_840-18delTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,598,808 control chromosomes in the GnomAD database, including 118,947 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8733 hom., cov: 0)
  • Exomes 𝑓: 0.39 (110214 hom.)
• Consequence: TBX6 NM_004608.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.610
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-30086868-GTGA-G is Benign according to our data. Variant chr16-30086868-GTGA-G is described in ClinVar as Benign. ClinVar VariationId is 259450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

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_840-18delTCA		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.840-20_840-18delTCA		intron	N/A	ENSP00000378650.2
	TBX6	ENST00000279386.6	TSL:1	c.840-20_840-18delTCA		intron	N/A	ENSP00000279386.2
	TBX6	ENST00000567664.5	TSL:5	n.*48-176_*48-174delTCA		intron	N/A	ENSP00000460425.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49335 AN: 151630 Hom.: 8737 Cov.: 0

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.365 AC: 81054 AN: 222238 AF XY: 0.375

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.383

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.387 AC: 559517 AN: 1447060 Hom.: 110214 AF XY: 0.388 AC XY: 279294 AN XY: 719034

African (AFR) AF: 0.165 AC: 5494 AN: 33288

American (AMR) AF: 0.292 AC: 12694 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9503 AN: 25898

East Asian (EAS) AF: 0.327 AC: 12870 AN: 39302

South Asian (SAS) AF: 0.439 AC: 37065 AN: 84462

European-Finnish (FIN) AF: 0.358 AC: 17908 AN: 49962

Middle Eastern (MID) AF: 0.290 AC: 1666 AN: 5738

European-Non Finnish (NFE) AF: 0.398 AC: 439910 AN: 1105172

Other (OTH) AF: 0.375 AC: 22407 AN: 59798

GnomAD4 genome AF: 0.325 AC: 49325 AN: 151748 Hom.: 8733 Cov.: 0 AF XY: 0.326 AC XY: 24135 AN XY: 74140

African (AFR) AF: 0.175 AC: 7242 AN: 41450

American (AMR) AF: 0.321 AC: 4902 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1855 AN: 5134

South Asian (SAS) AF: 0.434 AC: 2081 AN: 4800

European-Finnish (FIN) AF: 0.366 AC: 3847 AN: 10516

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26958 AN: 67828

Other (OTH) AF: 0.318 AC: 670 AN: 2106

Alfa AF: 0.288 Hom.: 1171

Bravo AF: 0.308

Asia WGS AF: 0.323 AC: 1127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Spondylocostal dysostosis 5 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3833842; hg19: chr16-30098189;