chr16-1362287-A-AC
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_032520.5(GNPTG):c.499dup(p.Leu167ProfsTer32) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T165T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032520.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTG | NM_032520.5 | c.499dup | p.Leu167ProfsTer32 | frameshift_variant | 7/11 | ENST00000204679.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTG | ENST00000204679.9 | c.499dup | p.Leu167ProfsTer32 | frameshift_variant | 7/11 | 1 | NM_032520.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 151942Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249592Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135324
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1460942Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 726826
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151942Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74200
ClinVar
Submissions by phenotype
GNPTG-mucolipidosis Pathogenic:7
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2000 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 21, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Aug 01, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Jun 18, 2017 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The frame shift c.499dupC (p.Leu167Profs32) variant has been reported previously in homozygous state in several individuals affected with mucolipidosis III (Tüysüz B et al.,2017). The p.L167Pfs32 variant is observed in (0.0125%) alleles from individuals of African background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to ClinVar database as Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | This sequence change creates a premature translational stop signal (p.Leu167Profs*32) in the GNPTG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTG are known to be pathogenic (PMID: 19370764, 20301784). This variant is present in population databases (rs756959430, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with mucolipidosis III (PMID: 29170090). ClinVar contains an entry for this variant (Variation ID: 437454). 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