17-42536295-CGGCGGT-C

Position:

• chr17-42536295-CGGCGGT-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000263.4(NAGLU):​c.26_31delCGGTGG​(p.Ala9_Val10del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAGLU NM_000263.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAGLU	NM_000263.4	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	1/6	ENST00000225927.7	NP_000254.2
NAGLU	XM_024450771.2	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	1/7		XP_024306539.1
NAGLU	XM_047436138.1	c.-436_-431delCGGTGG		5_prime_UTR_variant	1/5		XP_047292094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAGLU	ENST00000225927.7	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	1/6	1	NM_000263.4	ENSP00000225927.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-B Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Mar 06, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555621405; hg19: chr17-40688313;