rs1060500751
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005585.5(SMAD6):c.318_320delCGTinsAGG(p.AspVal106GluGly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SMAD6
NM_005585.5 missense
NM_005585.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.563
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.318_320delCGTinsAGG | p.AspVal106GluGly | missense_variant | ENST00000288840.10 | NP_005576.3 | ||
SMAD6 | NR_027654.2 | n.1341_1343delCGTinsAGG | non_coding_transcript_exon_variant | 1/5 | ||||
SMAD6 | XR_931827.3 | n.1341_1343delCGTinsAGG | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.318_320delCGTinsAGG | p.AspVal106GluGly | missense_variant | 1 | NM_005585.5 | ENSP00000288840.5 | |||
SMAD6 | ENST00000557916.5 | n.318_320delCGTinsAGG | non_coding_transcript_exon_variant | 1/5 | 1 | ENSP00000452955.1 | ||||
SMAD6 | ENST00000612349.1 | n.500_502delCGTinsAGG | non_coding_transcript_exon_variant | 1/1 | 6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aortic valve disease 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 30, 2016 | This sequence change deletes 3 nucleotides and inserts 3 in exon 1 of the SMAD6 mRNA (c.318_320delinsAGG). This leads to the deletion of 2 amino acid residues in the SMAD6 protein and the insertion of glutamic acid and glycine (p.Asp106_Val107delinsGluGly) but otherwise preserves the integrity of the reading frame. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. Experimental studies evaluating the effect of this in-frame deletion have not been published. In summary, this is a novel in-frame change with an unknown effect on protein function. For these reasons it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at