rs34428684

Variant names:

• chr12-114682517-CTTTT-C
• rs34428684
• NM_005996.4:c.389+291_389+294delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr12-114682517-CTTTT-C
• chr12-114682517-CTTTT-CT
• chr12-114682517-CTTTT-CTT
• chr12-114682517-CTTTT-CTTT
• chr12-114682517-CTTTT-CTTTTT
• chr12-114682517-CTTTT-CTTTTTT
• chr12-114682517-CTTTT-CTTTTTTTTTT
• chr12-114682517-CTTTT-CTTTTTTTTTTT
• chr12-114682517-CTTTT-CTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005996.4(TBX3):​c.389+291_389+294delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 145,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00019 (0 hom., cov: 31)
• Consequence: TBX3 NM_005996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000192 (28/145548) while in subpopulation AFR AF = 0.00065 (26/39996). AF 95% confidence interval is 0.000455. There are 0 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 28 AD gene.

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+291_389+294delAAAA		intron	N/A	NP_005987.3
	TBX3	NM_016569.4		c.389+291_389+294delAAAA		intron	N/A	NP_057653.3
	TBX3-AS1	NR_187552.1		n.235_238delTTTT		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+291_389+294delAAAA		intron	N/A	ENSP00000257567.2	O15119-2
	TBX3	ENST00000257566.7	TSL:1	c.389+291_389+294delAAAA		intron	N/A	ENSP00000257566.3	O15119-1
	TBX3-AS1	ENST00000660721.1		n.235_238delTTTT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000186 AC: 27 AN: 145518 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000626

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000686

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: 0.0000151

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000192 AC: 28 AN: 145548 Hom.: 0 Cov.: 31 AF XY: 0.000226 AC XY: 16 AN XY: 70682

African (AFR) AF: 0.000650 AC: 26 AN: 39996

American (AMR) AF: 0.0000686 AC: 1 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 66006

Other (OTH) AF: 0.00 AC: 0 AN: 2014

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

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;