16-1354725-T-C

Variant names:

• chr16-1354725-T-C
• rs761057
• NM_032520.5:c.178+2419T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032520.5(GNPTG):​c.178+2419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,228 control chromosomes in the GnomAD database, including 64,987 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 0.92 (64987 hom., cov: 32)
• Consequence: GNPTG NM_032520.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 11 publications found

Genes affected

GNPTG (HGNC:23026): (N-acetylglucosamine-1-phosphate transferase subunit gamma) This gene encodes the gamma sunbunit of the N-acetylglucosamine-1-phosphotransferase complex. This hexameric complex, composed of alpha, beta and gamma subunits, catalyzes the first step in synthesis of a mannose 6-phosphate lysosomal recognition marker. This enzyme complex is necessary for targeting of lysosomal hydrolases to the lysosome. Mutations in the gene encoding the gamma subunit have been associated with mucolipidosis IIIC, also known as mucolipidosis III gamma.[provided by RefSeq, Feb 2010]

GNPTG Gene-Disease associations (from GenCC):

• GNPTG-mucolipidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032520.5. 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
	GNPTG	NM_032520.5	MANE Select	c.178+2419T>C		intron	N/A	NP_115909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTG	ENST00000204679.9	TSL:1 MANE Select	c.178+2419T>C		intron	N/A	ENSP00000204679.4
	GNPTG	ENST00000529110.2	TSL:2	c.262+2419T>C		intron	N/A	ENSP00000435349.2
	GNPTG	ENST00000683887.1		c.178+2419T>C		intron	N/A	ENSP00000506886.1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140424 AN: 152110 Hom.: 64927 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.923 AC: 140543 AN: 152228 Hom.: 64987 Cov.: 32 AF XY: 0.927 AC XY: 68995 AN XY: 74428

African (AFR) AF: 0.964 AC: 40049 AN: 41530

American (AMR) AF: 0.935 AC: 14296 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3056 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.943 AC: 4550 AN: 4826

European-Finnish (FIN) AF: 0.931 AC: 9857 AN: 10586

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60473 AN: 68010

Other (OTH) AF: 0.934 AC: 1976 AN: 2116

Alfa AF: 0.905 Hom.: 41803

Bravo AF: 0.925

Asia WGS AF: 0.978 AC: 3402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs761057; hg19: chr16-1404726;