15-67066146-TC-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000327367.9(SMAD3):c.-5del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SMAD3
ENST00000327367.9 5_prime_UTR
ENST00000327367.9 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.106
Genes affected
SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.-5del | 5_prime_UTR_variant | 1/9 | ENST00000327367.9 | NP_005893.1 | ||
SMAD3 | NM_001407011.1 | c.-5del | 5_prime_UTR_variant | 1/10 | NP_001393940.1 | |||
SMAD3 | NM_001407012.1 | c.-5del | 5_prime_UTR_variant | 1/8 | NP_001393941.1 | |||
SMAD3 | NM_001407013.1 | c.-5del | 5_prime_UTR_variant | 1/8 | NP_001393942.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367.9 | c.-5del | 5_prime_UTR_variant | 1/9 | 1 | NM_005902.4 | ENSP00000332973 | P1 | ||
SMAD3 | ENST00000560424.2 | c.-5del | 5_prime_UTR_variant | 1/10 | 3 | ENSP00000455540 | ||||
SMAD3 | ENST00000559460.6 | c.-110+2206del | intron_variant | 4 | ENSP00000453082 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.00e-7 AC: 1AN: 1428582Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 707870
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1428582
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Cov.:
32
AF XY:
AC XY:
0
AN XY:
707870
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aneurysm-osteoarthritis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | This variant deletes one nucleotide in the 3' untranslated region of the SMAD3 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SMAD3-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.