rs1006328829
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3
The NM_001378454.1(ALMS1):c.69_70insAAG(p.Glu23_Glu24insLys) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E23E) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
ALMS1
NM_001378454.1 inframe_insertion
NM_001378454.1 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.190
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 Likely_benign. Variant got -1 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_001378454.1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.69_70insAAG | p.Glu23_Glu24insLys | inframe_insertion | 1/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.69_70insAAG | p.Glu23_Glu24insLys | inframe_insertion | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.69_70insAAG | p.Glu23_Glu24insLys | inframe_insertion | 1/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 13
GnomAD4 exome
Cov.:
13
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Asia WGS
AF:
AC:
4
AN:
3474
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This variant, c.72_73insAAG, results in the insertion of 1 amino acid(s) of the ALMS1 protein (p.Glu24_Glu25insLys), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). 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: 551340). 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, criteria provided, single submitter | clinical testing | Counsyl | Mar 31, 2017 | - - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at