14-75958704-TAAAA-TAAAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_003239.5(TGFB3):c.*482dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 174,170 control chromosomes in the GnomAD database, including 16 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 31)

Exomes 𝑓: 0.044 ( 0 hom. )

Consequence

TGFB3
NM_003239.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

0 publications found

Variant links:

Genes affected

TGFB3 (HGNC:11769): (transforming growth factor beta 3) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]

TGFB3 links:

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IFT43 Gene-Disease associations (from GenCC):

cranioectodermal dysplasia 3
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
short-rib thoracic dysplasia 18 with polydactyly
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
retinitis pigmentosa 81
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

IFT43 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0112 (1583/140768) while in subpopulation SAS AF = 0.0359 (153/4266). AF 95% confidence interval is 0.0312. There are 16 homozygotes in GnomAd4. There are 777 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AD,AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003239.5. 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
	TGFB3	NM_003239.5	MANE Select	c.*482dupT		3_prime_UTR	Exon 7 of 7	NP_003230.1	A5YM40
	TGFB3	NM_001329939.2		c.*482dupT		3_prime_UTR	Exon 8 of 8	NP_001316868.1	A5YM40

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGFB3	ENST00000238682.8	TSL:1 MANE Select	c.*482dupT	3_prime_UTR	Exon 7 of 7	ENSP00000238682.3	P10600-1
TGFB3	ENST00000964917.1		c.*482dupT	3_prime_UTR	Exon 8 of 8	ENSP00000634976.1
TGFB3	ENST00000556674.2	TSL:3	c.*482dupT	3_prime_UTR	Exon 8 of 8	ENSP00000502685.1	P10600-1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1575

AN:

140738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.000607

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.0355

Gnomad FIN

AF:

0.00864

Gnomad MID

AF:

0.00987

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00937

GnomAD4 exome

AF:

0.0439

AC:

1467

AN:

33402

Hom.:

Cov.:

AF XY:

0.0443

AC XY:

758

AN XY:

17102

show subpopulations

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

African (AFR)

AF:

0.0444

AC:

AN:

834

American (AMR)

AF:

0.0425

AC:

134

AN:

3152

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

AN:

642

East Asian (EAS)

AF:

0.0434

AC:

AN:

2214

South Asian (SAS)

AF:

0.0589

AC:

214

AN:

3634

European-Finnish (FIN)

AF:

0.0467

AC:

AN:

964

Middle Eastern (MID)

AF:

0.0303

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.0414

AC:

833

AN:

20100

Other (OTH)

AF:

0.0434

AC:

AN:

1730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.329

Heterozygous variant carriers

131

263

394

526

657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0112

AC:

1583

AN:

140768

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

777

AN XY:

68290

show subpopulations

African (AFR)

AF:

0.0260

AC:

995

AN:

38260

American (AMR)

AF:

0.00535

AC:

AN:

14008

Ashkenazi Jewish (ASJ)

AF:

0.000607

AC:

AN:

3296

East Asian (EAS)

AF:

0.0108

AC:

AN:

4902

South Asian (SAS)

AF:

0.0359

AC:

153

AN:

4266

European-Finnish (FIN)

AF:

0.00864

AC:

AN:

8680

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00325

AC:

209

AN:

64280

Other (OTH)

AF:

0.00933

AC:

AN:

1930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00113

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over