rs761584357

Variant names:

• chr16-1362108-C-T
• rs761584357
• NM_032520.5:c.388C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1362108-C-T
• chr16-1362108-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032520.5(GNPTG):​c.388C>T​(p.Arg130Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,459,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R130H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GNPTG NM_032520.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 6.64
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.388C>T	p.Arg130Cys	missense	Exon 6 of 11	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.388C>T	p.Arg130Cys	missense	Exon 6 of 11	ENSP00000204679.4	Q9UJJ9
	GNPTG	ENST00000891792.1		c.508C>T	p.Arg170Cys	missense	Exon 7 of 12	ENSP00000561851.1
	GNPTG	ENST00000529110.2	TSL:2	c.472C>T	p.Arg158Cys	missense	Exon 5 of 10	ENSP00000435349.2	H0YEA7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246192 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1459996 Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 726270

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52638

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111424

Other (OTH) AF: 0.0000166 AC: 1 AN: 60298

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	GNPTG-mucolipidosis (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.6
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.29
Sift	Benign	0.11	T
Sift4G	Uncertain	0.047	D
Polyphen		0.013	B
Vest4		0.41
MutPred		0.49		Loss of MoRF binding (P = 0.0038)
MVP		0.83
MPC		0.0063
ClinPred		0.38	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.48
Mutation Taster		=91/9	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: rs761584357; hg19: chr16-1412109;