Genetic Variant TBX3:c.389+294dupA (chr12-114682517-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.457

Publications

0 publications found

Variant links:

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 links:

TBX3-AS1 (HGNC:55471): (TBX3 antisense RNA 1)

TBX3-AS1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

AF XY:

0.0349

AC XY:

2464

AN XY:

70606

show subpopulations

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:

AN:

5018

South Asian (SAS)

AF:

0.00529

AC:

AN:

4538

European-Finnish (FIN)

AF:

0.0253

AC:

222

AN:

8776

Middle Eastern (MID)

AF:

0.0180

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0260

AC:

1713

AN:

65948

Other (OTH)

AF:

0.0253

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

234

469

703

938

1172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.0365

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over