rs7963747

Positions:

• chr12-101768326-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000299314.12(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 ENST00000299314.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTAB	NM_024312.5	c.1285-166G>A		intron_variant		ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4	c.1285-166G>A		intron_variant			XP_006719656.1
GNPTAB	XM_011538731.3	c.1204-166G>A		intron_variant			XP_011537033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12	c.1285-166G>A		intron_variant		1	NM_024312.5	ENSP00000299314	P1
GNPTAB	ENST00000549940.5	c.1285-166G>A		intron_variant		1		ENSP00000449150

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

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.583

Alfa AF: 0.560 Hom.: 4067

Bravo AF: 0.580

Asia WGS AF: 0.773 AC: 2684 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.021
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs7963747; hg19: chr12-102162104;