12-114678547-T-A

Variant names:

• chr12-114678547-T-A
• rs59336
• NM_005996.4:c.805-891A>T

Variant summary

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

The NM_005996.4(TBX3):​c.805-891A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,918 control chromosomes in the GnomAD database, including 18,534 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 0.49 (18534 hom., cov: 32)
• Consequence: TBX3 NM_005996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• Publications: 38 publications found

Genes affected

TBX3 (HGNC:11602): (T-box transcription factor 3) 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. This protein is a transcriptional repressor and is thought to play a role in the anterior/posterior axis of the tetrapod forelimb. Mutations in this gene cause ulnar-mammary syndrome, affecting limb, apocrine gland, tooth, hair, and genital development. Alternative splicing of this gene results in three transcript variants encoding different isoforms; however, the full length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]

TBX3 Gene-Disease associations (from GenCC):

• ulnar-mammary syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX3	NM_005996.4	c.805-891A>T		intron_variant	Intron 3 of 6	ENST00000349155.7	NP_005987.3
TBX3	NM_016569.4	c.865-891A>T		intron_variant	Intron 4 of 7		NP_057653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX3	ENST00000349155.7	c.805-891A>T		intron_variant	Intron 3 of 6	1	NM_005996.4	ENSP00000257567.2
TBX3	ENST00000257566.7	c.865-891A>T		intron_variant	Intron 4 of 7	1		ENSP00000257566.3
TBX3	ENST00000548503.1	n.430-891A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74777 AN: 151800 Hom.: 18532 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.492 AC: 74793 AN: 151918 Hom.: 18534 Cov.: 32 AF XY: 0.486 AC XY: 36095 AN XY: 74228

African (AFR) AF: 0.519 AC: 21492 AN: 41440

American (AMR) AF: 0.426 AC: 6497 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1691 AN: 3464

East Asian (EAS) AF: 0.362 AC: 1864 AN: 5146

South Asian (SAS) AF: 0.462 AC: 2220 AN: 4808

European-Finnish (FIN) AF: 0.472 AC: 4972 AN: 10542

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34540 AN: 67948

Other (OTH) AF: 0.495 AC: 1043 AN: 2108

Alfa AF: 0.499 Hom.: 2371

Bravo AF: 0.490

Asia WGS AF: 0.414 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.79
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: rs59336; hg19: chr12-115116352;