rs955371491
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001378454.1(ALMS1):āc.103G>Cā(p.Ala35Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 1,526,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
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.103G>C | p.Ala35Pro | missense_variant | 1/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.106G>C | p.Ala36Pro | missense_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.103G>C | p.Ala35Pro | missense_variant | 1/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000673 AC: 1AN: 148504Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 79074
GnomAD4 exome AF: 0.00000437 AC: 6AN: 1374372Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 679242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 18, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 36 of the ALMS1 protein (p.Ala36Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 403920). 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2023 | The p.A36P variant (also known as c.106G>C), located in coding exon 1 of the ALMS1 gene, results from a G to C substitution at nucleotide position 106. The alanine at codon 36 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at