17-42536274-T-TGGAGGC

Variant summary

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

The NM_000263.4(NAGLU):c.5_10dup(p.Glu2_Ala3dup) variant causes a inframe insertion 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)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAGLU NM_000263.4 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.984

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	UniProt
NAGLU	NM_000263.4	c.5_10dup	p.Glu2_Ala3dup	inframe_insertion	1/6	ENST00000225927.7
NAGLU	XM_024450771.2	c.5_10dup	p.Glu2_Ala3dup	inframe_insertion	1/7
NAGLU	XM_047436138.1	c.-457_-452dup		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAGLU	ENST00000225927.7	c.5_10dup	p.Glu2_Ala3dup	inframe_insertion	1/6	1	NM_000263.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000188 AC: 2 AN: 1064954 Hom.: 0 Cov.: 30 AF XY: 0.00000398 AC XY: 2 AN XY: 502992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000220

Gnomad4 OTH exome AF: 0.00

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

Sep 27, 2017

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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: rs1555621396; hg19: chr17-40688292;