rs281864999
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_024312.5(GNPTAB):βc.2691_2693delβ(p.Lys898del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000149 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. K897K) has been classified as Likely benign.
Frequency
Genomes: π 0.000026 ( 0 hom., cov: 32)
Exomes π: 0.000014 ( 0 hom. )
Consequence
GNPTAB
NM_024312.5 inframe_deletion
NM_024312.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.49
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_024312.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.2691_2693del | p.Lys898del | inframe_deletion | 13/21 | ENST00000299314.12 | |
GNPTAB | XM_006719593.4 | c.2691_2693del | p.Lys898del | inframe_deletion | 13/19 | ||
GNPTAB | XM_011538731.3 | c.2610_2612del | p.Lys871del | inframe_deletion | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.2691_2693del | p.Lys898del | inframe_deletion | 13/21 | 1 | NM_024312.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152056Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461672Hom.: 0 AF XY: 0.0000124 AC XY: 9AN XY: 727152
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74422
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 26, 2017 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at