2-216482755-GATC-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_014140.4(SMARCAL1):c.2644_2646delATC(p.Ile882del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014140.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCAL1 | NM_014140.4 | c.2644_2646delATC | p.Ile882del | conservative_inframe_deletion | Exon 18 of 18 | ENST00000357276.9 | NP_054859.2 | |
SMARCAL1 | NM_001127207.2 | c.2644_2646delATC | p.Ile882del | conservative_inframe_deletion | Exon 18 of 18 | NP_001120679.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461878Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:4
This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.004% (3/68036) (https://gnomad.broadinstitute.org/variant/2-216482755-GATC-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:1060525). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 1 amino acid at position 882 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In addition, although this variant occurs in the exon, splice prediction tools suggest that this variant may impact splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
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This variant, c.2644_2646del, results in the deletion of 1 amino acid(s) of the SMARCAL1 protein (p.Ile882del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1060525). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at