16-1354725-T-C

Position:

• chr16-1354725-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPTG	NM_032520.5	c.178+2419T>C		intron_variant		ENST00000204679.9	NP_115909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPTG	ENST00000204679.9	c.178+2419T>C		intron_variant		1	NM_032520.5	ENSP00000204679.4

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

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.934

Alfa AF: 0.903 Hom.: 28406

Bravo AF: 0.925

Asia WGS AF: 0.978 AC: 3402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.50

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: rs761057; hg19: chr16-1404726;