rs7963747

Variant names:

• chr12-101768326-C-T
• rs7963747
• NM_024312.5:c.1285-166G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024312.5(GNPTAB):​c.1285-166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,150 control chromosomes in the GnomAD database, including 26,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (26445 hom., cov: 33)
• Consequence: GNPTAB NM_024312.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25
• Publications: 10 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-101768326-C-T is Benign according to our data. Variant chr12-101768326-C-T is described in ClinVar as Benign. ClinVar VariationId is 671996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

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.1285-166G>A		intron	N/A	NP_077288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	ENST00000299314.12	TSL:1 MANE Select	c.1285-166G>A		intron	N/A	ENSP00000299314.7
	GNPTAB	ENST00000549940.5	TSL:1	c.1285-166G>A		intron	N/A	ENSP00000449150.1
	GNPTAB	ENST00000552009.1	TSL:3	n.-223G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88741 AN: 152032 Hom.: 26411 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.584 AC: 88833 AN: 152150 Hom.: 26445 Cov.: 33 AF XY: 0.590 AC XY: 43870 AN XY: 74396

African (AFR) AF: 0.637 AC: 26427 AN: 41498

American (AMR) AF: 0.541 AC: 8276 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1958 AN: 3470

East Asian (EAS) AF: 0.896 AC: 4650 AN: 5192

South Asian (SAS) AF: 0.642 AC: 3092 AN: 4818

European-Finnish (FIN) AF: 0.641 AC: 6777 AN: 10570

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35666 AN: 67994

Other (OTH) AF: 0.583 AC: 1233 AN: 2114

Alfa AF: 0.561 Hom.: 4212

Bravo AF: 0.580

Asia WGS AF: 0.773 AC: 2684 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.021
DANN	Benign	0.59
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7963747; hg19: chr12-102162104;