chr2-73449529-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001378454.1(ALMS1):c.3002G>T(p.Gly1001Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,794 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1001D) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.3002G>T | p.Gly1001Val | missense_variant | 8/23 | ENST00000613296.6 | |
ALMS1 | NM_015120.4 | c.3005G>T | p.Gly1002Val | missense_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.3002G>T | p.Gly1001Val | missense_variant | 8/23 | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248348Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134736
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461772Hom.: 0 Cov.: 40 AF XY: 0.00000413 AC XY: 3AN XY: 727186
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74250
ClinVar
Submissions by phenotype
Alstrom syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs773630367 in Alstrom syndrome yet. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1002 of the ALMS1 protein (p.Gly1002Val). This variant is present in population databases (rs773630367, gnomAD 0.003%). 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: 570836). 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. - |
Monogenic diabetes Benign:1
Likely benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Jan 11, 2019 | ACMG criteria: BP4 (0.088 + 9 predictors), BP1 (missense in gene where truncating primarily cause disease)= likely benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at