rs886051373
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_005902.4(SMAD3):c.-265T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 216,020 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_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD3 | NM_005902.4 | c.-265T>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 9 | ENST00000327367.9 | NP_005893.1 | ||
SMAD3 | NM_005902.4 | c.-265T>G | 5_prime_UTR_variant | Exon 1 of 9 | ENST00000327367.9 | NP_005893.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD3 | ENST00000327367 | c.-265T>G | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 9 | 1 | NM_005902.4 | ENSP00000332973.4 | |||
SMAD3 | ENST00000327367 | c.-265T>G | 5_prime_UTR_variant | Exon 1 of 9 | 1 | NM_005902.4 | ENSP00000332973.4 |
Frequencies
GnomAD3 genomes AF: 0.000152 AC: 23AN: 151282Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.000402 AC: 26AN: 64738Hom.: 0 Cov.: 0 AF XY: 0.000420 AC XY: 13AN XY: 30926
GnomAD4 genome AF: 0.000152 AC: 23AN: 151282Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 73894
ClinVar
Submissions by phenotype
Aneurysm-osteoarthritis syndrome Uncertain:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at