rs200814417
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001378454.1(ALMS1):c.12227G>A(p.Arg4076Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4076W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.12227G>A | p.Arg4076Gln | missense_variant | 20/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.12230G>A | p.Arg4077Gln | missense_variant | 20/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.12227G>A | p.Arg4076Gln | missense_variant | 20/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251436Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135884
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 727242
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74484
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4077 of the ALMS1 protein (p.Arg4077Gln). This variant is present in population databases (rs200814417, gnomAD 0.004%). 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: 434135). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 02, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at