GeneBe

rs1024697806

Variant names:

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.644

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • mucopolysaccharidosis type 3B
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Myriad Women’s Health
  • Charcot-Marie-Tooth disease axonal type 2V
    Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
NAGLUNM_000263.4 linkc.15_20delGGTGGC p.Val6_Ala7del disruptive_inframe_deletion Exon 1 of 6 ENST00000225927.7 NP_000254.2
NAGLUXM_024450771.2 linkc.15_20delGGTGGC p.Val6_Ala7del disruptive_inframe_deletion Exon 1 of 7 XP_024306539.1
NAGLUXM_047436138.1 linkc.-447_-442delGGTGGC 5_prime_UTR_variant Exon 1 of 5 XP_047292094.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAGLUENST00000225927.7 linkc.15_20delGGTGGC p.Val6_Ala7del disruptive_inframe_deletion Exon 1 of 6 1 NM_000263.4 ENSP00000225927.1
NAGLUENST00000586516.5 linkc.-246_-241delGGCGGT upstream_gene_variant 2 ENSP00000467135.1
NAGLUENST00000591587.1 linkc.-252_-247delGGCGGT upstream_gene_variant 5 ENSP00000467836.1
ENSG00000266929ENST00000585572.1 linkn.-232_-227delGGCGGT upstream_gene_variant 4

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
show subpopulations
⚠️ 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.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.64

Splicing

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

Publications

Other links and lift over

dbSNP: rs1024697806; hg19: chr17-40688295; API