rs193922318
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000162.5(GCK):c.666C>T(p.Val222Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,832 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000162.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152140Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251426Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135908
GnomAD4 exome AF: 0.000104 AC: 152AN: 1461692Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 76AN XY: 727156
GnomAD4 genome AF: 0.000105 AC: 16AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
In silico analysis suggests this variant may impact gene splicing; in the absence of RNA/functional studies the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge -
- -
not specified Benign:2
- -
- -
Transient Neonatal Diabetes, Recessive Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Maturity-onset diabetes of the young type 2 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Type 2 diabetes mellitus;C0342277:Maturity-onset diabetes of the young type 2;C1865290:Hyperinsulinism due to glucokinase deficiency Uncertain:1
- -
Maturity onset diabetes mellitus in young Uncertain:1
The c.666C>T variant (also known as p.V222V), located in coding exon 6 of the GCK gene, results from a C to T substitution at nucleotide position 666. This nucleotide substitution does not change the at codon 222. This variant was previously identified in one individual with maturity-onset diabetes of the young. In vitro studies using mini-gene constructs showed this alteration can introduce an alternate splice donor site that would result in the deletion of 16 nucleotides from exon 6 in the RNA transcript (Igudin E et al. Mol. Biol. (Mosk.) 2014;48(2):288-94). In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site. This nucleotide position is poorly conserved in available vertebrate species with thymine being the reference nucleotide in several species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Permanent neonatal diabetes mellitus Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Hyperinsulinism due to glucokinase deficiency Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at