2-73451503-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001378454.1(ALMS1):c.4976C>A(p.Pro1659Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.4976C>A | p.Pro1659Gln | missense_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.4979C>A | p.Pro1660Gln | missense_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.4976C>A | p.Pro1659Gln | missense_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151840Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 249012Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135146
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461804Hom.: 0 Cov.: 38 AF XY: 0.0000110 AC XY: 8AN XY: 727210
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151958Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74296
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 1660 of the ALMS1 protein (p.Pro1660Gln). This variant is present in population databases (rs199520788, gnomAD 0.09%). 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: 529389). 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at