rs764039432
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001378454.1(ALMS1):c.5074C>T(p.Pro1692Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. 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. P1692L) has been classified as Uncertain significance.
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.5074C>T | p.Pro1692Ser | missense_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.5077C>T | p.Pro1693Ser | missense_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.5074C>T | p.Pro1692Ser | missense_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249254Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135228
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461816Hom.: 0 Cov.: 39 AF XY: 0.0000234 AC XY: 17AN XY: 727208
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74210
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 29, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1693 of the ALMS1 protein (p.Pro1693Ser). This variant is present in population databases (rs764039432, gnomAD 0.04%). 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: 576922). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at