rs919214

Positions:

• chr12-101776999-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024312.5(GNPTAB):​c.771+3153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,248 control chromosomes in the GnomAD database, including 2,732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2732 hom., cov: 32)
• Consequence: GNPTAB NM_024312.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTAB	NM_024312.5	c.771+3153G>A		intron_variant		ENST00000299314.12	NP_077288.2
GNPTAB	XM_011538731.3	c.690+3153G>A		intron_variant			XP_011537033.1
GNPTAB	XM_006719593.4	c.771+3153G>A		intron_variant			XP_006719656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12	c.771+3153G>A		intron_variant		1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5	c.771+3153G>A		intron_variant		1		ENSP00000449150.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28286 AN: 152130 Hom.: 2726 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.186 AC: 28307 AN: 152248 Hom.: 2732 Cov.: 32 AF XY: 0.186 AC XY: 13859 AN XY: 74442

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.183

Alfa AF: 0.194 Hom.: 4146

Bravo AF: 0.189

Asia WGS AF: 0.208 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs919214; hg19: chr12-102170777;