rs757734472
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001378454.1(ALMS1):βc.11045_11056delβ(p.Leu3682_Ser3685del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000020 ( 0 hom., cov: 32)
Exomes π: 6.8e-7 ( 0 hom. )
Consequence
ALMS1
NM_001378454.1 inframe_deletion
NM_001378454.1 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.12
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001378454.1.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.11045_11056del | p.Leu3682_Ser3685del | inframe_deletion | 16/23 | ENST00000613296.6 | NP_001365383.1 | |
ALMS1 | NM_015120.4 | c.11048_11059del | p.Leu3683_Ser3686del | inframe_deletion | 16/23 | NP_055935.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.11045_11056del | p.Leu3682_Ser3685del | inframe_deletion | 16/23 | 1 | NM_001378454.1 | ENSP00000482968 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249296Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135292
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461268Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726962
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74286
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 28, 2021 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 09, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 16, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at