NM_024312.5:c.-47_-39delGGCGGCGGC

Variant names:

• chr12-101830713-AGCCGCCGCC-A
• rs76300806
• NM_024312.5:c.-47_-39delGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 5 publications found

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]

GNPTAB Gene-Disease associations (from GenCC):

• GNPTAB-mucolipidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mucolipidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• mucolipidosis type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• mucolipidosis type III, alpha/beta

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024312.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	NM_024312.5	MANE Select	c.-47_-39delGGCGGCGGC		5_prime_UTR	Exon 1 of 21	NP_077288.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	ENST00000299314.12	TSL:1 MANE Select	c.-47_-39delGGCGGCGGC		5_prime_UTR	Exon 1 of 21	ENSP00000299314.7	Q3T906-1
	GNPTAB	ENST00000549940.5	TSL:1	c.-47_-39delGGCGGCGGC		5_prime_UTR	Exon 1 of 11	ENSP00000449150.1	Q3T906-2
	GNPTAB	ENST00000392919.4	TSL:1	c.-47_-39delGGCGGCGGC		5_prime_UTR	Exon 1 of 3	ENSP00000376651.4	Q9BUA5

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

GnomAD2 exomes AF: 0.000961 AC: 151 AN: 157184 AF XY: 0.000906

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 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

African (AFR) AF: 0.000848 AC: 15 AN: 17692

American (AMR) AF: 0.00128 AC: 45 AN: 35182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20934

East Asian (EAS) AF: 0.0000659 AC: 2 AN: 30350

South Asian (SAS) AF: 0.0000869 AC: 6 AN: 69024

European-Finnish (FIN) AF: 0.000234 AC: 11 AN: 47030

Middle Eastern (MID) AF: 0.00129 AC: 4 AN: 3096

European-Non Finnish (NFE) AF: 0.00160 AC: 1014 AN: 634270

Other (OTH) AF: 0.00120 AC: 48 AN: 39900

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

African (AFR) AF: 0.000754 AC: 31 AN: 41108

American (AMR) AF: 0.00152 AC: 23 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5014

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.0000989 AC: 1 AN: 10112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00165 AC: 110 AN: 66666

Other (OTH) AF: 0.00241 AC: 5 AN: 2076

Alfa AF: 0.000627 Hom.: 2213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=296/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs76300806; hg19: chr12-102224491;