rs764135588
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378454.1(ALMS1):c.3980C>T(p.Pro1327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 150300Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249208Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135178
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461826Hom.: 0 Cov.: 40 AF XY: 0.0000110 AC XY: 8AN XY: 727218
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 150300Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73372
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:4
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This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1328 of the ALMS1 protein (p.Pro1328Leu). This variant is present in population databases (rs764135588, gnomAD 0.0009%). 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: 570871). 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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not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at