chr2-73448047-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001378454.1(ALMS1):c.1520G>C(p.Gly507Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G507G) has been classified as Likely benign.
Frequency
Consequence
NM_001378454.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.1520G>C | p.Gly507Ala | missense_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.1523G>C | p.Gly508Ala | missense_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.1520G>C | p.Gly507Ala | missense_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2017 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; Align-GVGD: "Class C0". This sequence change replaces glycine with alanine at codon 508 of the ALMS1 protein (p.Gly508Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ALMS1-related disease. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at