12-114682517-CTTTT-CTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005996.4(TBX3):​c.389+294dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 145,412 control chromosomes in the GnomAD database, including 108 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.036 (108 hom., cov: 31)
• Consequence: TBX3 NM_005996.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-114682517-C-CT is Benign according to our data. Variant chr12-114682517-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1234843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

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+294dupA		intron	N/A	NP_005987.3
	TBX3	NM_016569.4		c.389+294dupA		intron	N/A	NP_057653.3
	TBX3-AS1	NR_187552.1		n.238dupT		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+294dupA		intron	N/A	ENSP00000257567.2	O15119-2
	TBX3	ENST00000257566.7	TSL:1	c.389+294dupA		intron	N/A	ENSP00000257566.3	O15119-1
	TBX3-AS1	ENST00000660721.1		n.238dupT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5229 AN: 145384 Hom.: 108 Cov.: 31

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.0389

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.00517

Gnomad SAS AF: 0.00548

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0166

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0255

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

GnomAD4 genome AF: 0.0361 AC: 5243 AN: 145412 Hom.: 108 Cov.: 31 AF XY: 0.0349 AC XY: 2464 AN XY: 70606

African (AFR) AF: 0.0698 AC: 2791 AN: 39978

American (AMR) AF: 0.0157 AC: 228 AN: 14566

Ashkenazi Jewish (ASJ) AF: 0.0436 AC: 148 AN: 3398

East Asian (EAS) AF: 0.00518 AC: 26 AN: 5018

South Asian (SAS) AF: 0.00529 AC: 24 AN: 4538

European-Finnish (FIN) AF: 0.0253 AC: 222 AN: 8776

Middle Eastern (MID) AF: 0.0180 AC: 5 AN: 278

European-Non Finnish (NFE) AF: 0.0260 AC: 1713 AN: 65948

Other (OTH) AF: 0.0253 AC: 51 AN: 2012

Alfa AF: 0.00391 Hom.: 0

Bravo AF: 0.0365

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;