rs144929410

Variant names:

• chr16-1361832-C-T
• rs144929410
• NM_032520.5:c.233+35C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032520.5(GNPTG):​c.233+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,613,716 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: GNPTG NM_032520.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.99
• Publications: 1 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: Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-1361832-C-T is Benign according to our data. Variant chr16-1361832-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 262082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00162 (246/152246) while in subpopulation NFE AF = 0.00297 (202/68022). AF 95% confidence interval is 0.00263. There are 1 homozygotes in GnomAd4. There are 112 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTG	NM_032520.5	MANE Select	c.233+35C>T		intron	N/A	NP_115909.1	Q9UJJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTG	ENST00000204679.9	TSL:1 MANE Select	c.233+35C>T		intron	N/A	ENSP00000204679.4	Q9UJJ9
	GNPTG	ENST00000891792.1		c.353+35C>T		intron	N/A	ENSP00000561851.1
	GNPTG	ENST00000529110.2	TSL:2	c.317+35C>T		intron	N/A	ENSP00000435349.2	H0YEA7

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152128 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00152 AC: 382 AN: 251168 AF XY: 0.00155

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.00280

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00273 AC: 3994 AN: 1461470 Hom.: 6 Cov.: 33 AF XY: 0.00271 AC XY: 1971 AN XY: 727058

African (AFR) AF: 0.000478 AC: 16 AN: 33438

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86256

European-Finnish (FIN) AF: 0.000826 AC: 44 AN: 53244

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00335 AC: 3729 AN: 1111814

Other (OTH) AF: 0.00245 AC: 148 AN: 60394

GnomAD4 genome AF: 0.00162 AC: 246 AN: 152246 Hom.: 1 Cov.: 33 AF XY: 0.00150 AC XY: 112 AN XY: 74444

African (AFR) AF: 0.000482 AC: 20 AN: 41530

American (AMR) AF: 0.000588 AC: 9 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 68022

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00171

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.042
DANN	Benign	0.81
PhyloP100		-6.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism

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: rs144929410; hg19: chr16-1411833;