chr12-101745531-AG-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_024312.5(GNPTAB):c.*1632del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 152,360 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0031 ( 6 hom., cov: 33)
Failed GnomAD Quality Control
Consequence
GNPTAB
NM_024312.5 3_prime_UTR
NM_024312.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.137
Genes affected
GNPTAB (HGNC:29670): (N-acetylglucosamine-1-phosphate transferase subunits alpha and beta) This gene encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved at the Lys928-Asp929 bond to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GeneID 84572). In the Golgi apparatus, the heterohexameric complex catalyzes the first step in the synthesis of mannose 6-phosphate recognition markers on certain oligosaccharides of newly synthesized lysosomal enzymes. These recognition markers are essential for appropriate trafficking of lysosomal enzymes. Mutations in this gene have been associated with both mucolipidosis II and mucolipidosis IIIA.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00312 (475/152360) while in subpopulation AFR AF= 0.0104 (433/41598). AF 95% confidence interval is 0.0096. There are 6 homozygotes in gnomad4. There are 229 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.*1632del | 3_prime_UTR_variant | 21/21 | ENST00000299314.12 | ||
GNPTAB | XM_011538731.3 | c.*1632del | 3_prime_UTR_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.*1632del | 3_prime_UTR_variant | 21/21 | 1 | NM_024312.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00303 AC: 461AN: 152244Hom.: 1 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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GnomAD4 genome AF: 0.00312 AC: 475AN: 152360Hom.: 6 Cov.: 33 AF XY: 0.00307 AC XY: 229AN XY: 74522
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mucolipidosis, Type III Alpha/Beta Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Mucolipidosis type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at