chr12-101765328-A-AT

Position:

• chr12-101765328-A-AT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_024312.5(GNPTAB):​c.1613-25dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,435,622 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (15 hom.)
• Consequence: GNPTAB NM_024312.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.155

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 12-101765328-A-AT is Benign according to our data. Variant chr12-101765328-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 558794.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00508 (6529/1285110) while in subpopulation NFE AF= 0.00579 (5582/964776). AF 95% confidence interval is 0.00566. There are 15 homozygotes in gnomad4_exome. There are 3140 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.
• 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.1613-25dupA		intron_variant		ENST00000299314.12	NP_077288.2
GNPTAB	XM_011538731.3	c.1532-25dupA		intron_variant			XP_011537033.1
GNPTAB	XM_006719593.4	c.1613-25dupA		intron_variant			XP_006719656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12	c.1613-25dupA		intron_variant		1	NM_024312.5	ENSP00000299314.7

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 403 AN: 150402 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00617

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00418

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.00508 AC: 6529 AN: 1285110 Hom.: 15 Cov.: 20 AF XY: 0.00487 AC XY: 3140 AN XY: 644550

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.000479

Gnomad4 ASJ exome AF: 0.000839

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.00163

Gnomad4 FIN exome AF: 0.00984

Gnomad4 NFE exome AF: 0.00579

Gnomad4 OTH exome AF: 0.00335

GnomAD4 genome AF: 0.00266 AC: 401 AN: 150512 Hom.: 2 Cov.: 33 AF XY: 0.00272 AC XY: 200 AN XY: 73416

Gnomad4 AFR AF: 0.000706

Gnomad4 AMR AF: 0.000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.00617

Gnomad4 NFE AF: 0.00416

Gnomad4 OTH AF: 0.000963

Bravo AF: 0.00203

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

May 10, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs546802775; hg19: chr12-102159106;