rs10444509

chr12-101820252-T-C

Variant summary

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

The NM_024312.5(GNPTAB):c.117+10307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,204 control chromosomes in the GnomAD database, including 2,562 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 0.18 (2562 hom., cov: 32)
• Consequence: GNPTAB NM_024312.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNPTAB	NM_024312.5	c.117+10307A>G		intron_variant		ENST00000299314.12
GNPTAB	XM_006719593.4	c.117+10307A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPTAB	ENST00000299314.12	c.117+10307A>G		intron_variant		1	NM_024312.5	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27454 AN: 152086 Hom.: 2562 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.180 AC: 27462 AN: 152204 Hom.: 2562 Cov.: 32 AF XY: 0.180 AC XY: 13420 AN XY: 74406

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.170

Alfa AF: 0.171 Hom.: 4471

Bravo AF: 0.178

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.0
Dann	Benign	0.52

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: rs10444509; hg19: chr12-102214030;