rs1024697806

Variant names:

• chr17-42536277-AGGCGGT-A
• rs1024697806
• NM_000263.4:c.15_20delGGTGGC

Your query was ambiguous. Multiple possible variants found:

• chr17-42536277-AGGCGGT-A
• chr17-42536277-AGGCGGT-AGGCGGTGGCGGT

Variant summary

Our verdict is Uncertain significance. The variant received 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. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: NAGLU NM_000263.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• 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: Genomics England PanelApp, Myriad Women’s Health, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease axonal type 2V

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

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.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 6	NP_000254.2	A0A140VJE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGLU	ENST00000225927.7	TSL:1 MANE Select	c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000225927.1	P54802
	NAGLU	ENST00000963429.1		c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000633488.1
	NAGLU	ENST00000904921.1		c.15_20delGGTGGC	p.Val6_Ala7del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000574980.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1065536 Hom.: 0 AF XY: 0.00000397 AC XY: 2 AN XY: 503220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22282

American (AMR) AF: 0.00 AC: 0 AN: 7906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13646

East Asian (EAS) AF: 0.00 AC: 0 AN: 25286

South Asian (SAS) AF: 0.00 AC: 0 AN: 19408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2830

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 910856

Other (OTH) AF: 0.00 AC: 0 AN: 42602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64

Splicing

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

Other links and lift over

dbSNP: rs1024697806; hg19: chr17-40688295;