chr12-101830713-AGCCGCC-A

Variant names:

• chr12-101830713-AGCCGCC-A
• rs76300806
• NM_024312.5:c.-44_-39delGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• mucolipidosis type III, alpha/beta

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	NM_024312.5	MANE Select	c.-44_-39delGGCGGC		5_prime_UTR	Exon 1 of 21	NP_077288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	ENST00000299314.12	TSL:1 MANE Select	c.-44_-39delGGCGGC		5_prime_UTR	Exon 1 of 21	ENSP00000299314.7
	GNPTAB	ENST00000549940.5	TSL:1	c.-44_-39delGGCGGC		5_prime_UTR	Exon 1 of 11	ENSP00000449150.1
	GNPTAB	ENST00000392919.4	TSL:1	c.-44_-39delGGCGGC		5_prime_UTR	Exon 1 of 3	ENSP00000376651.4

Frequencies

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

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

GnomAD2 exomes AF: 0.000248 AC: 39 AN: 157184 AF XY: 0.000184

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00121 AC: 21 AN: 17404

American (AMR) AF: 0.000546 AC: 19 AN: 34830

Ashkenazi Jewish (ASJ) AF: 0.000241 AC: 5 AN: 20770

East Asian (EAS) AF: 0.00111 AC: 33 AN: 29656

South Asian (SAS) AF: 0.000161 AC: 11 AN: 68424

European-Finnish (FIN) AF: 0.0000429 AC: 2 AN: 46614

Middle Eastern (MID) AF: 0.000653 AC: 2 AN: 3062

European-Non Finnish (NFE) AF: 0.000339 AC: 214 AN: 631244

Other (OTH) AF: 0.000404 AC: 16 AN: 39566

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 40980

American (AMR) AF: 0.00 AC: 0 AN: 15078

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66674

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.00194 Hom.: 2213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=294/6	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;