12-101830713-AGCCGCCGCCGCC-AGCCGCC

Position:

• chr12-101830713-AGCCGCCGCCGCC-AGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024312.5(GNPTAB):​c.-44_-39delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 891,570 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNPTAB NM_024312.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTAB	NM_024312.5	c.-44_-39delGGCGGC		5_prime_UTR_variant	1/21	ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4	c.-44_-39delGGCGGC		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.-44_-39delGGCGGC		5_prime_UTR_variant	1/21	1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5	c.-44_-39delGGCGGC		5_prime_UTR_variant	1/11	1		ENSP00000449150.1
GNPTAB	ENST00000392919.4	c.-44_-39delGGCGGC		5_prime_UTR_variant	1/3	1		ENSP00000376651.4
GNPTAB	ENST00000549165.1	c.-44_-39delGGCGGC		upstream_gene_variant		1		ENSP00000450413.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149334 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000248 AC: 39 AN: 157184 Hom.: 0 AF XY: 0.000184 AC XY: 16 AN XY: 87190

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.000252

Gnomad ASJ exome AF: 0.000123

Gnomad EAS exome AF: 0.000977

Gnomad SAS exome AF: 0.000175

Gnomad FIN exome AF: 0.0000631

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000470

GnomAD4 exome AF: 0.000362 AC: 323 AN: 891570 Hom.: 0 AF XY: 0.000336 AC XY: 155 AN XY: 461874

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.000546

Gnomad4 ASJ exome AF: 0.000241

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.0000429

Gnomad4 NFE exome AF: 0.000339

Gnomad4 OTH exome AF: 0.000404

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149334 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72672

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;