12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCC

Position:

• chr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_024312.5(GNPTAB):​c.-47_-39dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: GNPTAB NM_024312.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTAB	NM_024312.5	c.-47_-39dupGGCGGCGGC		5_prime_UTR_variant	1/21	ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4	c.-47_-39dupGGCGGCGGC		5_prime_UTR_variant	1/19		XP_006719656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12	c.-47_-39dupGGCGGCGGC		5_prime_UTR_variant	1/21	1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5	c.-47_-39dupGGCGGCGGC		5_prime_UTR_variant	1/11	1		ENSP00000449150.1
GNPTAB	ENST00000392919.4	c.-47_-39dupGGCGGCGGC		5_prime_UTR_variant	1/3	1		ENSP00000376651.4
GNPTAB	ENST00000549165.1	c.-47_-39dupGGCGGCGGC		upstream_gene_variant		1		ENSP00000450413.1

Frequencies

GnomAD3 genomes AF: 0.0000670 AC: 10 AN: 149358 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000323 AC: 29 AN: 897542 Hom.: 0 Cov.: 0 AF XY: 0.0000280 AC XY: 13 AN XY: 464972

Gnomad4 AFR exome AF: 0.0000565

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000145

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.0000752

GnomAD4 genome AF: 0.0000669 AC: 10 AN: 149464 Hom.: 0 Cov.: 0 AF XY: 0.0000824 AC XY: 6 AN XY: 72800

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.000265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000198

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76300806; hg19: chr12-102224491;