rs104893985
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_000434.4(NEU1):c.239C>T(p.Pro80Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P80T) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000434.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEU1 | NM_000434.4 | c.239C>T | p.Pro80Leu | missense_variant | 2/6 | ENST00000375631.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEU1 | ENST00000375631.5 | c.239C>T | p.Pro80Leu | missense_variant | 2/6 | 1 | NM_000434.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000244 AC: 6AN: 246260Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134352
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460726Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726676
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
Sialidosis type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2002 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 80 of the NEU1 protein (p.Pro80Leu). This variant is present in population databases (rs104893985, gnomAD 0.02%). This missense change has been observed in individual(s) with sialidosis (PMID: 11829139, 23291686, 32472645, 34476202). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2452). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NEU1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NEU1 function (PMID: 11829139). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at