12-114682517-CTTTT-CTTT

Variant names:

• chr12-114682517-CT-C
• rs34428684
• NM_005996.4:c.389+294delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005996.4(TBX3):​c.389+294delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 145,260 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0011 (0 hom., cov: 31)
• Consequence: TBX3 NM_005996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 0 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-AS1 (HGNC:55471): (TBX3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005996.4. 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
	TBX3	NM_005996.4	MANE Select	c.389+294delA		intron	N/A	NP_005987.3
	TBX3	NM_016569.4		c.389+294delA		intron	N/A	NP_057653.3
	TBX3-AS1	NR_187552.1		n.238delT		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX3	ENST00000349155.7	TSL:1 MANE Select	c.389+294delA		intron	N/A	ENSP00000257567.2	O15119-2
	TBX3	ENST00000257566.7	TSL:1	c.389+294delA		intron	N/A	ENSP00000257566.3	O15119-1
	TBX3-AS1	ENST00000660721.1		n.238delT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 159 AN: 145230 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000927

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.00132

Gnomad FIN AF: 0.00263

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.00300

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

GnomAD4 genome AF: 0.00111 AC: 161 AN: 145260 Hom.: 0 Cov.: 31 AF XY: 0.00125 AC XY: 88 AN XY: 70522

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000926 AC: 37 AN: 39976

American (AMR) AF: 0.00103 AC: 15 AN: 14558

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3398

East Asian (EAS) AF: 0.00140 AC: 7 AN: 5010

South Asian (SAS) AF: 0.00154 AC: 7 AN: 4536

European-Finnish (FIN) AF: 0.00263 AC: 23 AN: 8746

Middle Eastern (MID) AF: 0.00719 AC: 2 AN: 278

European-Non Finnish (NFE) AF: 0.000942 AC: 62 AN: 65850

Other (OTH) AF: 0.00349 AC: 7 AN: 2008

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs34428684; hg19: chr12-115120322; COSMIC: COSV57469115; COSMIC: COSV57469115;