NAGLU p.Tyr558Tyr

Variant names:

• chr17-42543677-C-C
• NM_000263.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-42543678--
• chr17-42543680-C-T

Variant summary

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

The NM_000263.4(NAGLU):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAGLU NM_000263.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

NAGLU (HGNC:7632): (N-acetyl-alpha-glucosaminidase) This gene encodes an enzyme that degrades heparan sulfate by hydrolysis of terminal N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides. Defects in this gene are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB), also known as Sanfilippo syndrome B. This disease is characterized by the lysosomal accumulation and urinary excretion of heparan sulfate. [provided by RefSeq, Jul 2008]

NAGLU Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 3B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women's Health, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, G2P, Orphanet
• Charcot-Marie-Tooth disease axonal type 2V

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000266929 (HGNC:):

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_000263.4. 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
	NAGLU	NM_000263.4	MANE Select	c.		exon_region	Exon 6 of 6	NP_000254.2	A0A140VJE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000266929	ENST00000585572.1	TSL:4	n.		intron	N/A
	NAGLU	ENST00000592454.1	TSL:2	c.		downstream_gene	N/A	ENSP00000468665.1	K7ESD7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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: chr17-40695695;