rs71402581

Variant names:

• chr16-5027394-TGGGAGGAGGGAGGA-T
• rs71402581
• NM_016256.4:c.1175-29_1175-16delTCCTCCCTCCTCCC

Your query was ambiguous. Multiple possible variants found:

• chr16-5027394-TGGGAGGAGGGAGGA-T
• chr16-5027394-TGGGAGGAGGGAGGA-TGGGAGGA
• chr16-5027394-TGGGAGGAGGGAGGA-TGGGAGGAGGGAGGAGGGAGGA
• chr16-5027394-TGGGAGGAGGGAGGA-TGGGAGGAGGGAGGAGGGAGGAGGGAGGA

Variant summary

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

The NM_016256.4(NAGPA):​c.1175-29_1175-16delTCCTCCCTCCTCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,504 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NAGPA NM_016256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

NAGPA (HGNC:17378): (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase) Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. This gene encodes the enzyme that catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal hydrolases. Commonly known as 'uncovering enzyme' or UCE, this enzyme removes N-acetyl-D-glucosamine (GlcNAc) residues from GlcNAc-alpha-P-mannose moieties and thereby produces the recognition marker. The encoded preproprotein is proteolytically processed by furin to generate the mature enzyme, a homotetramer of two disulfide-linked homodimers. Mutations in this gene are associated with developmental stuttering in human patients. [provided by RefSeq, Oct 2015]

ENSG00000267072 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAGPA	NM_016256.4	c.1175-29_1175-16delTCCTCCCTCCTCCC		intron_variant	Intron 7 of 9	ENST00000312251.8	NP_057340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAGPA	ENST00000312251.8	c.1175-29_1175-16delTCCTCCCTCCTCCC		intron_variant	Intron 7 of 9	1	NM_016256.4	ENSP00000310998.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457504 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 725240

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108638

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71402581; hg19: chr16-5077395;