12-64752752-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002076.4(GNS):c.198G>A(p.Pro66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,443,948 control chromosomes in the GnomAD database, including 277,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P66P) has been classified as Likely benign.
Frequency
Consequence
NM_002076.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNS | NM_002076.4 | c.198G>A | p.Pro66= | synonymous_variant | 2/14 | ENST00000258145.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNS | ENST00000258145.8 | c.198G>A | p.Pro66= | synonymous_variant | 2/14 | 1 | NM_002076.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.695 AC: 105697AN: 152032Hom.: 38235 Cov.: 32
GnomAD3 exomes AF: 0.641 AC: 157726AN: 245972Hom.: 52130 AF XY: 0.638 AC XY: 84886AN XY: 132960
GnomAD4 exome AF: 0.602 AC: 777176AN: 1291798Hom.: 239134 Cov.: 22 AF XY: 0.604 AC XY: 393305AN XY: 650962
GnomAD4 genome AF: 0.695 AC: 105795AN: 152150Hom.: 38282 Cov.: 32 AF XY: 0.696 AC XY: 51742AN XY: 74372
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-D Benign:6
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 03, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:3
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 20, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 04, 2016 | Variant summary: The c.198G>A (p.Pro66=) in GNS gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.0655 (75159/114750 chrs tested), indicating that it is an ancestral allele. The observed frequency exceeds the maximum expected allele frequency for a pathogenic GNS variant of 0.0011 suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign by a reputable database/clinical laboratory. Taking together, based on the prevalence in general population the variant was classified as Benign. - |
Sanfilippo syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at