2-73385955-TGCA-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001378454.1(ALMS1):βc.90_92delβ(p.Ala35del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,367,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. A30A) has been classified as Likely benign.
Frequency
Consequence
NM_001378454.1 inframe_deletion
Scores
Clinical Significance
Conservation
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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.90_92del | p.Ala35del | inframe_deletion | 1/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.93_95del | p.Ala36del | inframe_deletion | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.90_92del | p.Ala35del | inframe_deletion | 1/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000674 AC: 1AN: 148308Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 5AN: 1219080Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 608932
GnomAD4 genome AF: 0.00000674 AC: 1AN: 148432Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1AN XY: 72314
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | This variant, c.93_95del, results in the deletion of 1 amino acid(s) of the ALMS1 protein (p.Ala36del), 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: 550960). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 02, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2022 | The c.93_95delAGC variant (also known as p.A36del) is located in coding exon 1 of the ALMS1 gene. This variant results from an in-frame AGC deletion at nucleotide positions 93 to 95. This results in the in-frame deletion of an alanine at codon 36. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). 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