ENST00000553607.1:c.-288A>G

Variant names:

• chr16-30091481-T-C
• rs3809624
• ENST00000553607.1:c.-288A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000553607.1(TBX6):​c.-288A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 323,542 control chromosomes in the GnomAD database, including 17,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6425 hom., cov: 30)
  • Exomes 𝑓: 0.33 (10616 hom.)
• Consequence: TBX6 ENST00000553607.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.604
• Publications: 50 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 16-30091481-T-C is Benign according to our data. Variant chr16-30091481-T-C is described in ClinVar as Benign. ClinVar VariationId is 427808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553607.1. 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.-48-240A>G		intron	N/A	NP_004599.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	ENST00000553607.1	TSL:1	c.-288A>G		5_prime_UTR	Exon 1 of 5	ENSP00000461223.1	O95947-2
	TBX6	ENST00000395224.7	TSL:1 MANE Select	c.-48-240A>G		intron	N/A	ENSP00000378650.2	O95947-1
	TBX6	ENST00000931584.1		c.-288A>G		5_prime_UTR	Exon 1 of 8	ENSP00000601643.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39385 AN: 150622 Hom.: 6424 Cov.: 30

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.331 AC: 57279 AN: 172808 Hom.: 10616 Cov.: 0 AF XY: 0.327 AC XY: 29253 AN XY: 89520

African (AFR) AF: 0.0732 AC: 357 AN: 4880

American (AMR) AF: 0.325 AC: 2247 AN: 6910

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1833 AN: 6236

East Asian (EAS) AF: 0.584 AC: 7157 AN: 12252

South Asian (SAS) AF: 0.229 AC: 3031 AN: 13222

European-Finnish (FIN) AF: 0.405 AC: 4084 AN: 10094

Middle Eastern (MID) AF: 0.245 AC: 213 AN: 868

European-Non Finnish (NFE) AF: 0.327 AC: 35082 AN: 107414

Other (OTH) AF: 0.300 AC: 3275 AN: 10932

GnomAD4 genome AF: 0.261 AC: 39395 AN: 150734 Hom.: 6425 Cov.: 30 AF XY: 0.264 AC XY: 19436 AN XY: 73526

African (AFR) AF: 0.0682 AC: 2793 AN: 40966

American (AMR) AF: 0.288 AC: 4367 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1090 AN: 3462

East Asian (EAS) AF: 0.473 AC: 2370 AN: 5006

South Asian (SAS) AF: 0.231 AC: 1105 AN: 4774

European-Finnish (FIN) AF: 0.404 AC: 4187 AN: 10354

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22504 AN: 67718

Other (OTH) AF: 0.281 AC: 583 AN: 2078

Alfa AF: 0.309 Hom.: 3316

Bravo AF: 0.250

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		0.60
PromoterAI		0.069	Neutral
Mutation Taster		=300/0	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: rs3809624; hg19: chr16-30102802; COSMIC: COSV54223106; COSMIC: COSV54223106;