12-101746272-C-CCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024312.5(GNPTAB):c.*891_*892insAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,240 control chromosomes in the GnomAD database, including 874 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (873 hom., cov: 31)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: GNPTAB NM_024312.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.595

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 -10 ACMG points.

• BP6: Variant 12-101746272-C-CCT is Benign according to our data. Variant chr12-101746272-C-CCT is described in ClinVar as [Likely_benign]. Clinvar id is 306778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNPTAB	NM_024312.5	c.*891_*892insAG		3_prime_UTR_variant	21/21	ENST00000299314.12
GNPTAB	XM_011538731.3	c.*891_*892insAG		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPTAB	ENST00000299314.12	c.*891_*892insAG		3_prime_UTR_variant	21/21	1	NM_024312.5	P1

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 14937 AN: 152116 Hom.: 872 Cov.: 31

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.0981 AC: 14941 AN: 152234 Hom.: 873 Cov.: 31 AF XY: 0.0969 AC XY: 7215 AN XY: 74432

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0855

Gnomad4 FIN AF: 0.0873

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.121

Alfa AF: 0.112 Hom.: 132

Bravo AF: 0.103

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Mucolipidosis, Type III Alpha/Beta Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Mucolipidosis type II Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59855215; hg19: chr12-102140050;