rs74680081
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001042413.2(GLIS3):c.1092G>T(p.Pro364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,600,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P364P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042413.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLIS3 | NM_001042413.2 | c.1092G>T | p.Pro364= | synonymous_variant | 4/11 | ENST00000381971.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS3 | ENST00000381971.8 | c.1092G>T | p.Pro364= | synonymous_variant | 4/11 | 5 | NM_001042413.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00145 AC: 220AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000240 AC: 53AN: 220946Hom.: 0 AF XY: 0.000106 AC XY: 13AN XY: 122676
GnomAD4 exome AF: 0.000140 AC: 202AN: 1447724Hom.: 1 Cov.: 36 AF XY: 0.0000972 AC XY: 70AN XY: 720088
GnomAD4 genome ? AF: 0.00146 AC: 223AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105AN XY: 74486
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 02, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 21, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | GLIS3: BP4, BP7 - |
Neonatal diabetes mellitus with congenital hypothyroidism Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
GLIS3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 14, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at