16-30091481-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.604

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 427808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX6	NM_004608.4	c.-48-240A>G		intron_variant		ENST00000395224.7
TBX6	XM_011545926.4	c.-70A>G		5_prime_UTR_variant	1/9
TBX6	XM_047434551.1	c.-288A>G		5_prime_UTR_variant	1/8
TBX6	XR_007064904.1	n.54A>G		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX6	ENST00000553607.1	c.-288A>G		5_prime_UTR_variant	1/5	1
TBX6	ENST00000395224.7	c.-48-240A>G		intron_variant		1	NM_004608.4	P1

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

Gnomad4 AFR exome AF: 0.0732

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.300

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

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.281

Alfa AF: 0.308 Hom.: 2929

Bravo AF: 0.250

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	19
Dann	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809624; hg19: chr16-30102802; COSMIC: COSV54223106; COSMIC: COSV54223106;