GNPTG p.Ser102Ile

Variant names:

• chr16-1361943-G-T
• NM_032520.5:c.305G>T
• GNPTG p.Ser102Ile

Your query was ambiguous. Multiple possible variants found:

• chr16-1361943-G-T
• chr16-1361943-GT-TC
• chr16-1361943-GT-TA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032520.5(GNPTG):​c.305G>T​(p.Ser102Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GNPTG NM_032520.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.40
• Publications: 0 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: Orphanet, G2P, Myriad Women's Health, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

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.305G>T	p.Ser102Ile	missense	Exon 5 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.305G>T	p.Ser102Ile	missense	Exon 5 of 11	ENSP00000204679.4	Q9UJJ9
	GNPTG	ENST00000891792.1		c.425G>T	p.Ser142Ile	missense	Exon 6 of 12	ENSP00000561851.1
	GNPTG	ENST00000529110.2	TSL:2	c.389G>T	p.Ser130Ile	missense	Exon 4 of 10	ENSP00000435349.2	H0YEA7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	GNPTG-mucolipidosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		9.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Varity_R		0.67
gMVP		0.72

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1411944;

COSMIC: COSV107214846;

COSMIC: COSV107214846;