rs281864983
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024312.5(GNPTAB):βc.1959_1962delβ(p.Ser654ProfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. V653V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024312.5 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 |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.1959_1962del | p.Ser654ProfsTer2 | frameshift_variant | 13/21 | ENST00000299314.12 | |
GNPTAB | XM_006719593.4 | c.1959_1962del | p.Ser654ProfsTer2 | frameshift_variant | 13/19 | ||
GNPTAB | XM_011538731.3 | c.1878_1881del | p.Ser627ProfsTer2 | frameshift_variant | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.1959_1962del | p.Ser654ProfsTer2 | frameshift_variant | 13/21 | 1 | NM_024312.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251414Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461808Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727206
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Sep 19, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 39041). This premature translational stop signal has been observed in individual(s) with mucolipidosis (PMID: 19634183). This variant is present in population databases (rs281864983, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Ser654Profs*2) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). - |
Mucolipidosis type II Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 20, 2020 | - - |
GNPTAB-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Daryl Scott Lab, Baylor College of Medicine | Nov 10, 2023 | - - |
Abnormality of metabolism/homeostasis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Kariminejad - Najmabadi Pathology & Genetics Center | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at