chr7-44149773-G-A
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.Val222=) 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). Synonymous variant affecting the same amino acid position (i.e. V222V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000162.5 synonymous
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 |
---|---|---|---|---|---|---|---|
GCK | NM_000162.5 | c.666C>T | p.Val222= | synonymous_variant | 6/10 | ENST00000403799.8 | |
LOC105375258 | XR_927223.3 | n.304G>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCK | ENST00000403799.8 | c.666C>T | p.Val222= | synonymous_variant | 6/10 | 1 | NM_000162.5 | P1 |
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 specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 10, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 28, 2017 | - - |
Transient Neonatal Diabetes, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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. - |
Maturity onset diabetes mellitus in young Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2023 | 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. - |
Type 2 diabetes mellitus;C0342277:Maturity-onset diabetes of the young type 2;C1865290:Hyperinsulinism due to glucokinase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jan 14, 2023 | - - |
Permanent neonatal diabetes mellitus Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at