rs763288832
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001378454.1(ALMS1):βc.2683_2685delβ(p.Asp895del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000046 ( 0 hom., cov: 33)
Exomes π: 0.000036 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 inframe_deletion
NM_001378454.1 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.346
Genes affected
ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
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Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_001378454.1. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.2683_2685del | p.Asp895del | inframe_deletion | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.2686_2688del | p.Asp896del | inframe_deletion | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.2683_2685del | p.Asp895del | inframe_deletion | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 151914Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248890Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 134996
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461836Hom.: 0 AF XY: 0.0000330 AC XY: 24AN XY: 727222
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GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 151914Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74206
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 29, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2022 | This variant, c.2686_2688del, results in the deletion of 1 amino acid(s) of the ALMS1 protein (p.Asp896del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs763288832, gnomAD 0.008%). 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: 445673). 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 06, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 25, 2024 | The c.2686_2688delGAT (p.D896del) alteration is located in exon 8 (coding exon 8) of the ALMS1 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.2686 and c.2688, resulting in the deletion of <NA> residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at