chr13-36848580-CAT-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001127217.3(SMAD9):c.*94_*95del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,148,244 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 4 hom. )
Consequence
SMAD9
NM_001127217.3 3_prime_UTR
NM_001127217.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.317
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 nfe. gnomad4_exome allele frequency = 0.0014 (1399/995958) while in subpopulation NFE AF= 0.00178 (1224/688186). AF 95% confidence interval is 0.0017. There are 4 homozygotes in gnomad4_exome. There are 700 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 166 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD9 | NM_001127217.3 | c.*94_*95del | 3_prime_UTR_variant | 7/7 | ENST00000379826.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD9 | ENST00000379826.5 | c.*94_*95del | 3_prime_UTR_variant | 7/7 | 5 | NM_001127217.3 | P1 | ||
SMAD9 | ENST00000350148.10 | c.*94_*95del | 3_prime_UTR_variant | 6/6 | 1 | ||||
SMAD9 | ENST00000399275.7 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00109 AC: 166AN: 152168Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00140 AC: 1399AN: 995958Hom.: 4 AF XY: 0.00136 AC XY: 700AN XY: 516384
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GnomAD4 genome ? AF: 0.00109 AC: 166AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63AN XY: 74466
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at