15-67066145-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005902.4(SMAD3):c.-10C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,580,076 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 Uncertain significance (★★).
Frequency
Consequence
NM_005902.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 9 | ENST00000327367.9 | NP_005893.1 | ||
SMAD3 | NM_001407011.1 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 10 | NP_001393940.1 | |||
SMAD3 | NM_001407012.1 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 8 | NP_001393941.1 | |||
SMAD3 | NM_001407013.1 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 8 | NP_001393942.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 9 | 1 | NM_005902.4 | ENSP00000332973.4 | |||
SMAD3 | ENST00000560424 | c.-10C>T | 5_prime_UTR_variant | Exon 1 of 10 | 3 | ENSP00000455540.2 | ||||
SMAD3 | ENST00000559460.6 | c.-110+2201C>T | intron_variant | Intron 1 of 8 | 4 | ENSP00000453082.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151978Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1428098Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 707552
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74212
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
This variant causes a C to T nucleotide substitution at the -10 position in the 5' untranslated region in 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 been identified in 1/225934 chromosomes 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. -
Ehlers-Danlos syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at