rs1553409710
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001378454.1(ALMS1):βc.8349_8352delβ(p.Glu2784Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. K2783K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378454.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.8349_8352del | p.Glu2784Ter | frameshift_variant | 10/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.8352_8355del | p.Glu2785Ter | frameshift_variant | 10/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.8349_8352del | p.Glu2784Ter | frameshift_variant | 10/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460086Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726178
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 31, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 552234). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 25846608, 30064963). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu2785*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Oct 19, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at