1-2228771-A-AGGC
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_003036.4(SKI):c.12_14dup(p.Ala4dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000891 in 1,122,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 8.9e-7 ( 0 hom. )
Consequence
SKI
NM_003036.4 inframe_insertion
NM_003036.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.08
Genes affected
SKI (HGNC:10896): (SKI proto-oncogene) This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_003036.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.12_14dup | p.Ala4dup | inframe_insertion | 1/7 | ENST00000378536.5 | |
SKI | XM_005244775.4 | c.12_14dup | p.Ala4dup | inframe_insertion | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.12_14dup | p.Ala4dup | inframe_insertion | 1/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000704337.1 | n.137+1254_137+1256dup | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 8.91e-7 AC: 1AN: 1122318Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 549572
GnomAD4 exome
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1
AN:
1122318
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Cov.:
31
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0
AN XY:
549572
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Shprintzen-Goldberg syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2020 | This variant has not been reported in the literature in individuals with SKI-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.12_14dup, results in the insertion of 1 amino acid(s) to the SKI protein (p.Ala5dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Name
Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at