rs86312
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000263.4(NAGLU):c.2209C>A(p.Arg737Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,610,882 control chromosomes in the GnomAD database, including 367 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R737G) has been classified as Benign.
Frequency
Consequence
NM_000263.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAGLU | NM_000263.4 | c.2209C>A | p.Arg737Ser | missense_variant | 6/6 | ENST00000225927.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAGLU | ENST00000225927.7 | c.2209C>A | p.Arg737Ser | missense_variant | 6/6 | 1 | NM_000263.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0146 AC: 2221AN: 152000Hom.: 26 Cov.: 31
GnomAD3 exomes AF: 0.0184 AC: 4553AN: 247800Hom.: 67 AF XY: 0.0198 AC XY: 2659AN XY: 134278
GnomAD4 exome AF: 0.0197 AC: 28690AN: 1458764Hom.: 341 Cov.: 74 AF XY: 0.0202 AC XY: 14625AN XY: 725758
GnomAD4 genome ? AF: 0.0146 AC: 2220AN: 152118Hom.: 26 Cov.: 31 AF XY: 0.0153 AC XY: 1135AN XY: 74362
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 21, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | NAGLU: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2019 | - - |
Mucopolysaccharidosis, MPS-III-B Benign:3
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, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 08, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 23, 2013 | - - |
Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at