rs61737294
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000263.4(NAGLU):c.421T>A(p.Ser141Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,614,212 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts 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. S141F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000263.4 missense
Scores
Clinical Significance
Conservation
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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.421T>A | p.Ser141Thr | missense_variant | 2/6 | ENST00000225927.7 | |
NAGLU | XM_024450771.2 | c.478T>A | p.Ser160Thr | missense_variant | 3/7 | ||
NAGLU | XM_047436138.1 | c.-79+780T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAGLU | ENST00000225927.7 | c.421T>A | p.Ser141Thr | missense_variant | 2/6 | 1 | NM_000263.4 | P1 | |
NAGLU | ENST00000590358.1 | c.109T>A | p.Ser37Thr | missense_variant | 1/2 | 4 | |||
NAGLU | ENST00000586516.5 | c.133+780T>A | intron_variant | 2 | |||||
NAGLU | ENST00000591587.1 | c.126+780T>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0195 AC: 2964AN: 152220Hom.: 103 Cov.: 33
GnomAD3 exomes AF: 0.00510 AC: 1282AN: 251452Hom.: 42 AF XY: 0.00389 AC XY: 529AN XY: 135910
GnomAD4 exome AF: 0.00178 AC: 2601AN: 1461874Hom.: 74 Cov.: 29 AF XY: 0.00155 AC XY: 1125AN XY: 727232
GnomAD4 genome ? AF: 0.0195 AC: 2966AN: 152338Hom.: 103 Cov.: 33 AF XY: 0.0189 AC XY: 1405AN XY: 74492
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 25, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 21, 2015 | - - |
Mucopolysaccharidosis, MPS-III-B Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
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