rs193302849
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM4_SupportingPP5_Very_Strong
The NM_032520.5(GNPTG):βc.347_349delβ(p.Asn116del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. A114A) has been classified as Likely benign.
Frequency
Consequence
NM_032520.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTG | NM_032520.5 | c.347_349del | p.Asn116del | inframe_deletion | 6/11 | ENST00000204679.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTG | ENST00000204679.9 | c.347_349del | p.Asn116del | inframe_deletion | 6/11 | 1 | NM_032520.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000929 AC: 23AN: 247476Hom.: 0 AF XY: 0.0000744 AC XY: 10AN XY: 134420
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1460196Hom.: 0 AF XY: 0.0000509 AC XY: 37AN XY: 726402
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74382
ClinVar
Submissions by phenotype
GNPTG-mucolipidosis Pathogenic:4Other:1
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 25, 2024 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | curation | Laboratory of Medical Genetics, National & Kapodistrian University of Athens | Feb 01, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 23, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 30, 2022 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This variant, c.347_349del, results in the deletion of 1 amino acid(s) of the GNPTG protein (p.Asn116del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs774681948, gnomAD 0.02%). This variant has been observed in individuals with mucolipidosis type III (PMID: 15532026, 19370764, 29170090). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21715). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects GNPTG function (PMID: 15532026). For these reasons, this variant has been classified as Pathogenic. - |
Rod-cone dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Jan 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at