12-101830713-AGCCGCCGCCGCC-AGCC

Position:

• chr12-101830713-AGCCGCCGCCGCC-AGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024312.5(GNPTAB):​c.-47_-39delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,046,940 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (3 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTAB	NM_024312.5	c.-47_-39delGGCGGCGGC		5_prime_UTR_variant	1/21	ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4	c.-47_-39delGGCGGCGGC		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_-39delGGCGGCGGC		5_prime_UTR_variant	1/21	1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5	c.-47_-39delGGCGGCGGC		5_prime_UTR_variant	1/11	1		ENSP00000449150.1
GNPTAB	ENST00000392919.4	c.-47_-39delGGCGGCGGC		5_prime_UTR_variant	1/3	1		ENSP00000376651.4
GNPTAB	ENST00000549165.1	c.-47_-39delGGCGGCGGC		upstream_gene_variant		1		ENSP00000450413.1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 171 AN: 149356 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00153

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000989

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00243

GnomAD3 exomes AF: 0.000961 AC: 151 AN: 157184 Hom.: 1 AF XY: 0.000906 AC XY: 79 AN XY: 87190

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000874

Gnomad FIN exome AF: 0.000316

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00211

GnomAD4 exome AF: 0.00128 AC: 1145 AN: 897478 Hom.: 3 AF XY: 0.00119 AC XY: 553 AN XY: 464938

Gnomad4 AFR exome AF: 0.000848

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000659

Gnomad4 SAS exome AF: 0.0000869

Gnomad4 FIN exome AF: 0.000234

Gnomad4 NFE exome AF: 0.00160

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00114 AC: 171 AN: 149462 Hom.: 2 Cov.: 0 AF XY: 0.00114 AC XY: 83 AN XY: 72798

Gnomad4 AFR AF: 0.000754

Gnomad4 AMR AF: 0.00152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000989

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00241

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;