12-114670755-TAAC-T

Position:

• chr12-114670755-TAAC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005996.4(TBX3):​c.*1083_*1085del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 212,930 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: TBX3 NM_005996.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-114670755-TAAC-T is Benign according to our data. Variant chr12-114670755-TAAC-T is described in ClinVar as [Likely_benign]. Clinvar id is 307334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 404 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX3	NM_005996.4	c.*1083_*1085del		3_prime_UTR_variant	7/7	ENST00000349155.7
TBX3	NM_016569.4	c.*1083_*1085del		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX3	ENST00000349155.7	c.*1083_*1085del		3_prime_UTR_variant	7/7	1	NM_005996.4	P4
TBX3	ENST00000257566.7	c.*1083_*1085del		3_prime_UTR_variant	8/8	1		A1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152194 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000297 AC: 18 AN: 60618 Hom.: 0 AF XY: 0.000354 AC XY: 10 AN XY: 28232

Gnomad4 AFR exome AF: 0.00467

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000396

GnomAD4 genome AF: 0.00265 AC: 404 AN: 152312 Hom.: 1 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74502

Gnomad4 AFR AF: 0.00933

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ulnar-mammary syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs557346755; hg19: chr12-115108560;