rs76300806

chr12-101830713-AGCCGCCGCCGCC-Achr12-101830713-AGCCGCCGCCGCC-AGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCchr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

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

The NM_024312.5(GNPTAB):c.-50_-39del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,046,988 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 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000099 (0 hom.)
• 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	UniProt
GNPTAB	NM_024312.5	c.-50_-39del		5_prime_UTR_variant	1/21	ENST00000299314.12
GNPTAB	XM_006719593.4	c.-50_-39del		5_prime_UTR_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPTAB	ENST00000299314.12	c.-50_-39del		5_prime_UTR_variant	1/21	1	NM_024312.5	P1
GNPTAB	ENST00000392919.4	c.-50_-39del		5_prime_UTR_variant	1/3	1
GNPTAB	ENST00000549940.5	c.-50_-39del		5_prime_UTR_variant	1/11	1
GNPTAB	ENST00000549165.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.000201 AC: 30 AN: 149356 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000464

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00146

GnomAD3 exomes AF: 0.000210 AC: 33 AN: 157184 Hom.: 0 AF XY: 0.000138 AC XY: 12 AN XY: 87190

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000841

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000219

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000705

GnomAD4 exome AF: 0.0000992 AC: 89 AN: 897526 Hom.: 0 AF XY: 0.0000817 AC XY: 38 AN XY: 464966

Gnomad4 AFR exome AF: 0.000170

Gnomad4 AMR exome AF: 0.000654

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000329

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000473

Gnomad4 OTH exome AF: 0.000401

GnomAD4 genome AF: 0.000207 AC: 31 AN: 149462 Hom.: 0 Cov.: 0 AF XY: 0.000124 AC XY: 9 AN XY: 72800

Gnomad4 AFR AF: 0.000365

Gnomad4 AMR AF: 0.000464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00193

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;