rs193302853

Variant names:

• chr16-1362561-GGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC-G
• rs193302853
• NM_032520.5:c.609+28_610-16delGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_032520.5(GNPTG):​c.609+28_610-16delGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GNPTG NM_032520.5 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.957
• Publications: 2 publications found

Genes affected

GNPTG (HGNC:23026): (N-acetylglucosamine-1-phosphate transferase subunit gamma) This gene encodes the gamma sunbunit of the N-acetylglucosamine-1-phosphotransferase complex. This hexameric complex, composed of alpha, beta and gamma subunits, catalyzes the first step in synthesis of a mannose 6-phosphate lysosomal recognition marker. This enzyme complex is necessary for targeting of lysosomal hydrolases to the lysosome. Mutations in the gene encoding the gamma subunit have been associated with mucolipidosis IIIC, also known as mucolipidosis III gamma.[provided by RefSeq, Feb 2010]

GNPTG Gene-Disease associations (from GenCC):

• GNPTG-mucolipidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant 16-1362561-GGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC-G is Pathogenic according to our data. Variant chr16-1362561-GGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 21719.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPTG	NM_032520.5	c.609+28_610-16delGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC		intron_variant	Intron 8 of 10	ENST00000204679.9	NP_115909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPTG	ENST00000204679.9	c.609+28_610-16delGTGGGCCTGGCTGGGAGCTGGGTGCTGCCCCTGC		intron_variant	Intron 8 of 10	1	NM_032520.5	ENSP00000204679.4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

GNPTG-mucolipidosis Pathogenic:1

Jul 05, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96
Mutation Taster		=37/63	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193302853; hg19: chr16-1412562;