2-73573291-GAATTA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001378454.1(ALMS1):c.11420_11424del(p.Lys3807IlefsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R3805R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378454.1 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.11420_11424del | p.Lys3807IlefsTer2 | frameshift_variant | 16/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.11423_11427del | p.Lys3808IlefsTer2 | frameshift_variant | 16/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.11420_11424del | p.Lys3807IlefsTer2 | frameshift_variant | 16/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248990Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135072
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461814Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727204
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 25, 2017 | This sequence change deletes 5 nucleotides from exon 16 of the ALMS1 mRNA (c.11423_11427delAATTA), causing a frameshift at codon 3808. This creates a premature translational stop signal (p.Lys3808Ilefs*2) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at