rs1184260245
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001378454.1(ALMS1):c.10272_10274delGAA(p.Lys3424del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001378454.1 disruptive_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 |
---|---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.10272_10274delGAA | p.Lys3424del | disruptive_inframe_deletion | Exon 15 of 23 | ENST00000613296.6 | NP_001365383.1 | |
ALMS1 | NM_015120.4 | c.10272_10274delGAA | p.Lys3424del | disruptive_inframe_deletion | Exon 15 of 23 | NP_055935.4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727194
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:4
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This variant, c.10275_10277del, results in the deletion of 1 amino acid(s) of the ALMS1 protein (p.Lys3425del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 550778). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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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Cardiovascular phenotype Uncertain:1
The c.10275_10277delGAA variant (also known as p.K3425del), located in coding exon 15 of the ALMS1 gene, results from an in-frame GAA deletion at nucleotide positions 10275 to 10277. This results in the in-frame deletion of a lysine at codon 3425. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at