16-1351956-C-T

Variant names:

• chr16-1351956-C-T
• rs1017797000
• NM_032520.5:c.-10C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032520.5(GNPTG):​c.-10C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,139,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: GNPTG NM_032520.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• 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]

TSR3 (HGNC:14175): (TSR3 ribosome maturation factor) Enables transferase activity. Involved in enzyme-directed rRNA pseudouridine synthesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_115909.1	Q9UJJ9
	GNPTG	NM_032520.5	MANE Select	c.-10C>T		5_prime_UTR	Exon 1 of 11	NP_115909.1	Q9UJJ9
	TSR3	NM_001001410.3	MANE Select	c.-152G>A		upstream_gene	N/A	NP_001001410.1	Q9UJK0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTG	ENST00000204679.9	TSL:1 MANE Select	c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000204679.4	Q9UJJ9
	GNPTG	ENST00000204679.9	TSL:1 MANE Select	c.-10C>T		5_prime_UTR	Exon 1 of 11	ENSP00000204679.4	Q9UJJ9
	GNPTG	ENST00000891785.1		c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000561844.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1139768 Hom.: 0 Cov.: 32 AF XY: 0.00000182 AC XY: 1 AN XY: 549150

African (AFR) AF: 0.00 AC: 0 AN: 22896

American (AMR) AF: 0.00 AC: 0 AN: 9522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15278

East Asian (EAS) AF: 0.00 AC: 0 AN: 25836

South Asian (SAS) AF: 0.0000287 AC: 1 AN: 34786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3122

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 957586

Other (OTH) AF: 0.0000217 AC: 1 AN: 46142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.95
PhyloP100		0.59
PromoterAI		0.0042	Neutral
Mutation Taster		=300/0	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: rs1017797000; hg19: chr16-1401957;