rs8060511

Variant names:

• chr16-30090275-C-A
• rs8060511
• NM_004608.4:c.353+483G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004608.4(TBX6):​c.353+483G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,960 control chromosomes in the GnomAD database, including 19,896 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19896 hom., cov: 31)
• Consequence: TBX6 NM_004608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX6	NM_004608.4	c.353+483G>T		intron_variant	Intron 3 of 8	ENST00000395224.7	NP_004599.2
TBX6	XM_011545926.4	c.353+483G>T		intron_variant	Intron 3 of 8		XP_011544228.1
TBX6	XM_047434551.1	c.353+483G>T		intron_variant	Intron 2 of 7		XP_047290507.1
TBX6	XR_007064904.1	n.476+483G>T		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX6	ENST00000395224.7	c.353+483G>T		intron_variant	Intron 3 of 8	1	NM_004608.4	ENSP00000378650.2
TBX6	ENST00000279386.6	c.353+483G>T		intron_variant	Intron 2 of 7	1		ENSP00000279386.2
TBX6	ENST00000553607.1	c.353+483G>T		intron_variant	Intron 2 of 4	1		ENSP00000461223.1
TBX6	ENST00000567664.5	n.353+483G>T		intron_variant	Intron 2 of 6	5		ENSP00000460425.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76530 AN: 151842 Hom.: 19870 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.504 AC: 76588 AN: 151960 Hom.: 19896 Cov.: 31 AF XY: 0.497 AC XY: 36942 AN XY: 74264

African (AFR) AF: 0.622 AC: 25779 AN: 41432

American (AMR) AF: 0.439 AC: 6706 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1900 AN: 5168

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4822

European-Finnish (FIN) AF: 0.405 AC: 4276 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32451 AN: 67920

Other (OTH) AF: 0.476 AC: 1002 AN: 2104

Alfa AF: 0.495 Hom.: 3045

Bravo AF: 0.508

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-1.2
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: rs8060511; hg19: chr16-30101596;