rs905373886
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378454.1(ALMS1):c.219C>G(p.Asp73Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,596,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D73A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1444162Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2AN XY: 716634
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
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This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 74 of the ALMS1 protein (p.Asp74Glu). 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 ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 403923). 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. -
Cardiovascular phenotype Uncertain:1
The p.D74E variant (also known as c.222C>G), located in coding exon 1 of the ALMS1 gene, results from a C to G substitution at nucleotide position 222. The aspartic acid at codon 74 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at