rs762452929
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001378454.1(ALMS1):c.7981G>A(p.Glu2661Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,088 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2661D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.7981G>A | p.Glu2661Lys | missense_variant | 10/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.7984G>A | p.Glu2662Lys | missense_variant | 10/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.7981G>A | p.Glu2661Lys | missense_variant | 10/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249426Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135320
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461882Hom.: 2 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 19, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2662 of the ALMS1 protein (p.Glu2662Lys). This variant is present in population databases (rs762452929, gnomAD 0.03%). 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: 459889). 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | May 06, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 21, 2022 | The p.E2662K variant (also known as c.7984G>A), located in coding exon 10 of the ALMS1 gene, results from a G to A substitution at nucleotide position 7984. The glutamic acid at codon 2662 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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