rs200959196
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001042413.2(GLIS3):c.1154G>T(p.Gly385Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,574,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G385S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042413.2 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 |
---|---|---|---|---|---|---|---|
GLIS3 | NM_001042413.2 | c.1154G>T | p.Gly385Val | missense_variant | 4/11 | ENST00000381971.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS3 | ENST00000381971.8 | c.1154G>T | p.Gly385Val | missense_variant | 4/11 | 5 | NM_001042413.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000205 AC: 36AN: 175834Hom.: 0 AF XY: 0.000164 AC XY: 16AN XY: 97470
GnomAD4 exome AF: 0.000300 AC: 427AN: 1422058Hom.: 0 Cov.: 36 AF XY: 0.000291 AC XY: 205AN XY: 704866
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74374
ClinVar
Submissions by phenotype
Neonatal diabetes mellitus with congenital hypothyroidism Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in GLIS3 predisposes to neonatal diabetes mellitus with an extra pancreatic manifestation of hypothyroidism. It also predisposes to early onset diabetes in adults.However no sufficient evidence is found to ascertain the role of this particular variant rs200959196, yet. - |
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Aug 01, 2017 | ACMG Criteria:BP4 (9 predictors) - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 230 of the GLIS3 protein (p.Gly230Val). This variant is present in population databases (rs200959196, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GLIS3-related conditions. ClinVar contains an entry for this variant (Variation ID: 549531). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at