rs878854609
Variant names:
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_003239.5(TGFB3):c.420G>A(p.Glu140Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
TGFB3
NM_003239.5 synonymous
NM_003239.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.91
Publications
0 publications found
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]
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 14-75971651-C-T is Benign according to our data. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-75971651-C-T is described in CliVar as Likely_benign. Clinvar id is 239521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TGFB3 | NM_003239.5 | c.420G>A | p.Glu140Glu | synonymous_variant | Exon 2 of 7 | ENST00000238682.8 | NP_003230.1 | |
| TGFB3 | NM_001329939.2 | c.420G>A | p.Glu140Glu | synonymous_variant | Exon 3 of 8 | NP_001316868.1 | ||
| TGFB3 | NM_001329938.2 | c.420G>A | p.Glu140Glu | synonymous_variant | Exon 2 of 5 | NP_001316867.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152248
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74386 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152248
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74386
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41456
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5208
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68046
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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2
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10
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30-35
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40-45
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Apr 15, 2016
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Rienhoff syndrome Benign:1
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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