dbSNP rs1024697806: NAGLU:p.Val6_Ala7del (chr17-42536277-AGGCGGT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_000263.4(NAGLU):c.15_20delGGTGGC(p.Val6_Ala7del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,065,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

NAGLU
NM_000263.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.644

Variant links:

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 links:

ENSG00000266929 (HGNC:):

ENSG00000266929 links:

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ACMG classification

Classification made for transcript

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 link	c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 6	ENST00000225927.7	NP_000254.2	P54802A0A140VJE4
NAGLU	XM_024450771.2 link	c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 7		XP_024306539.1
NAGLU	XM_047436138.1 link	c.-447_-442delGGTGGC		5_prime_UTR_variant	Exon 1 of 5		XP_047292094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAGLU	ENST00000225927.7 link	c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 6	1	NM_000263.4	ENSP00000225927.1	P54802
NAGLU	ENST00000586516.5 link	c.-246_-241delGGCGGT		upstream_gene_variant		2		ENSP00000467135.1	K7ENX5
NAGLU	ENST00000591587.1 link	c.-252_-247delGGCGGT		upstream_gene_variant		5		ENSP00000467836.1	K7EQH9
ENSG00000266929	ENST00000585572.1 link	n.-232_-227delGGCGGT		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000188

AC:

AN:

1065536

Hom.:

AF XY:

0.00000397

AC XY:

AN XY:

503220

show subpopulations

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over