rs201654702
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001378454.1(ALMS1):c.7577G>A(p.Gly2526Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G2526G) has been classified as Likely benign.
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.7577G>A | p.Gly2526Glu | missense_variant | 9/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.7580G>A | p.Gly2527Glu | missense_variant | 9/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.7577G>A | p.Gly2526Glu | missense_variant | 9/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249138Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135140
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727164
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 09, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 06, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2527 of the ALMS1 protein (p.Gly2527Glu). This variant is present in population databases (rs201654702, gnomAD 0.004%). 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: 552746). 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2023 | The p.G2527E variant (also known as c.7580G>A), located in coding exon 9 of the ALMS1 gene, results from a G to A substitution at nucleotide position 7580. The glycine at codon 2527 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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