12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCC

Position:

• chr12-101830713-AGCCGCCGCCGCC-AGCCGCCGCCGCCGCC

Variant summary

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

The NM_024312.5(GNPTAB):​c.-41_-39dupGGC 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 0.00056 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (1 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.-41_-39dupGGC		5_prime_UTR_variant	1/21	ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4	c.-41_-39dupGGC		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.-41_-39dupGGC		5_prime_UTR_variant	1/21	1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5	c.-41_-39dupGGC		5_prime_UTR_variant	1/11	1		ENSP00000449150.1
GNPTAB	ENST00000392919.4	c.-41_-39dupGGC		5_prime_UTR_variant	1/3	1		ENSP00000376651.4
GNPTAB	ENST00000549165.1	c.-41_-39dupGGC		upstream_gene_variant		1		ENSP00000450413.1

Frequencies

GnomAD3 genomes AF: 0.000502 AC: 75 AN: 149358 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000401 AC: 63 AN: 157184 Hom.: 1 AF XY: 0.000401 AC XY: 35 AN XY: 87190

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.000420

Gnomad ASJ exome AF: 0.000123

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.0000631

Gnomad NFE exome AF: 0.000206

Gnomad OTH exome AF: 0.000470

GnomAD4 exome AF: 0.000279 AC: 250 AN: 897536 Hom.: 1 Cov.: 0 AF XY: 0.000318 AC XY: 148 AN XY: 464970

Gnomad4 AFR exome AF: 0.000735

Gnomad4 AMR exome AF: 0.000625

Gnomad4 ASJ exome AF: 0.0000955

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.0000425

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.000150

GnomAD4 genome AF: 0.000555 AC: 83 AN: 149464 Hom.: 1 Cov.: 0 AF XY: 0.000632 AC XY: 46 AN XY: 72800

Gnomad4 AFR AF: 0.00141

Gnomad4 AMR AF: 0.000199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000240

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;