17-42536295-CGGCGGT-C

Variant names:

• chr17-42536295-CGGCGGT-C
• rs1555621405
• NM_000263.4:c.26_31delCGGTGG

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]

ENSG00000266929 (HGNC:):

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 rank	MANE	Protein	UniProt
NAGLU	NM_000263.4	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	Exon 1 of 6	ENST00000225927.7	NP_000254.2
NAGLU	XM_024450771.2	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	Exon 1 of 7		XP_024306539.1
NAGLU	XM_047436138.1	c.-436_-431delCGGTGG		5_prime_UTR_variant	Exon 1 of 5		XP_047292094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAGLU	ENST00000225927.7	c.26_31delCGGTGG	p.Ala9_Val10del	disruptive_inframe_deletion	Exon 1 of 6	1	NM_000263.4	ENSP00000225927.1
NAGLU	ENST00000586516.5	c.-228_-223delGGCGGT		upstream_gene_variant		2		ENSP00000467135.1
NAGLU	ENST00000591587.1	c.-234_-229delGGCGGT		upstream_gene_variant		5		ENSP00000467836.1
ENSG00000266929	ENST00000585572.1	n.-214_-209delGGCGGT		upstream_gene_variant		4

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

Mar 06, 2018

Counsyl

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;