13-36845100-ATG-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001127217.3(SMAD9):c.*3574_*3575del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 145,934 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.013 ( 22 hom., cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SMAD9
NM_001127217.3 3_prime_UTR
NM_001127217.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.685
Genes affected
SMAD9 (HGNC:6774): (SMAD family member 9) The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0134 (1954/145934) while in subpopulation SAS AF= 0.0468 (219/4678). AF 95% confidence interval is 0.0417. There are 22 homozygotes in gnomad4. There are 984 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 1954 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD9 | NM_001127217.3 | c.*3574_*3575del | 3_prime_UTR_variant | 7/7 | ENST00000379826.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD9 | ENST00000379826.5 | c.*3574_*3575del | 3_prime_UTR_variant | 7/7 | 5 | NM_001127217.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0134 AC: 1955AN: 145824Hom.: 22 Cov.: 30
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 2Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
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GnomAD4 genome AF: 0.0134 AC: 1954AN: 145934Hom.: 22 Cov.: 30 AF XY: 0.0138 AC XY: 984AN XY: 71076
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Pulmonary hypertension, primary, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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