2-73453903-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378454.1(ALMS1):āc.7376G>Cā(p.Ser2459Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2459G) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.7376G>C | p.Ser2459Thr | missense_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.7379G>C | p.Ser2460Thr | missense_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.7376G>C | p.Ser2459Thr | missense_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249154Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135150
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461796Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727196
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 09, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2022 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 2460 of the ALMS1 protein (p.Ser2460Thr). This variant is present in population databases (rs778055498, 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: 403936). 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. | Mar 31, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2019 | The p.S2460T variant (also known as c.7379G>C), located in coding exon 8 of the ALMS1 gene, results from a G to C substitution at nucleotide position 7379. The serine at codon 2460 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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