rs1060499687
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_024312.5(GNPTAB):c.3250-1_3250delinsAT variant causes a splice acceptor, coding sequence change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GNPTAB
NM_024312.5 splice_acceptor, coding_sequence
NM_024312.5 splice_acceptor, coding_sequence
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.14
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 Pathogenic. Variant got 13 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 12-101757657-GC-AT is Pathogenic according to our data. Variant chr12-101757657-GC-AT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 397570.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.3250-1_3250delinsAT | splice_acceptor_variant, coding_sequence_variant | 17/21 | ENST00000299314.12 | ||
GNPTAB | XM_006719593.4 | c.3250-1_3250delinsAT | splice_acceptor_variant, coding_sequence_variant | 17/19 | |||
GNPTAB | XM_011538731.3 | c.3169-1_3169delinsAT | splice_acceptor_variant, coding_sequence_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.3250-1_3250delinsAT | splice_acceptor_variant, coding_sequence_variant | 17/21 | 1 | NM_024312.5 | P1 | ||
GNPTAB | ENST00000550718.1 | c.62-1_62delinsAT | splice_acceptor_variant, coding_sequence_variant | 2/4 | 3 | ||||
GNPTAB | ENST00000549194.1 | n.116-1_116delinsAT | splice_acceptor_variant, non_coding_transcript_exon_variant | 2/3 | 3 | ||||
GNPTAB | ENST00000549738.5 | coding_sequence_variant, 5_prime_UTR_variant, NMD_transcript_variant | 1/5 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS | Jan 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at