rs763332859
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001378454.1(ALMS1):āc.8416T>Gā(p.Phe2806Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,410 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 (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.8416T>G | p.Phe2806Val | missense_variant | 10/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.8419T>G | p.Phe2807Val | missense_variant | 10/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.8416T>G | p.Phe2806Val | missense_variant | 10/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248518Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134910
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461180Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 726818
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74376
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 27, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2807 of the ALMS1 protein (p.Phe2807Val). This variant is present in population databases (rs763332859, 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: 459892). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2022 | The p.F2807V variant (also known as c.8419T>G), located in coding exon 10 of the ALMS1 gene, results from a T to G substitution at nucleotide position 8419. The phenylalanine at codon 2807 is replaced by valine, 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