rs1085307122
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_005585.5(SMAD6):c.1034del(p.Arg345ProfsTer194) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SMAD6
NM_005585.5 frameshift
NM_005585.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.87
Genes affected
SMAD6 (HGNC:6772): (SMAD family member 6) The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 27 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.1034del | p.Arg345ProfsTer194 | frameshift_variant | 4/4 | ENST00000288840.10 | |
SMAD6 | XM_011521561.3 | c.251del | p.Arg84ProfsTer194 | frameshift_variant | 4/4 | ||
SMAD6 | NR_027654.2 | n.2189del | non_coding_transcript_exon_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.1034del | p.Arg345ProfsTer194 | frameshift_variant | 4/4 | 1 | NM_005585.5 | P1 | |
SMAD6 | ENST00000557916.5 | c.*149del | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 1 | ||||
SMAD6 | ENST00000559931.5 | c.*149del | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CRANIOSYNOSTOSIS 7, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Apr 19, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at