rs45452795
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001378454.1(ALMS1):āc.10832A>Gā(p.Gln3611Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Q3611Q) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.10832A>G | p.Gln3611Arg | missense_variant | 16/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.10835A>G | p.Gln3612Arg | missense_variant | 16/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.10832A>G | p.Gln3611Arg | missense_variant | 16/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000523 AC: 13AN: 248778Hom.: 0 AF XY: 0.0000741 AC XY: 10AN XY: 134924
GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461766Hom.: 0 Cov.: 32 AF XY: 0.0000756 AC XY: 55AN XY: 727176
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 3612 of the ALMS1 protein (p.Gln3612Arg). This variant is present in population databases (rs45452795, 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: 403951). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 01, 2023 | The p.Q3612R variant (also known as c.10835A>G), located in coding exon 16 of the ALMS1 gene, results from an A to G substitution at nucleotide position 10835. The glutamine at codon 3612 is replaced by arginine, an amino acid with highly similar properties. This variant was detected in an individual with Alstrom syndrome; however, clinical details were limited, and the zygosity of the variant was not specified (Marshall JD et al. Hum Mutat, 2007 Nov;28:1114-23). 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