17-42537595-G-C

Variant names:

• chr17-42537595-G-C
• rs2071046
• NM_000263.4:c.531+50G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000263.4(NAGLU):​c.531+50G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,603,722 control chromosomes in the GnomAD database, including 428,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42250 hom., cov: 32)
  • Exomes 𝑓: 0.73 (386096 hom.)
• Consequence: NAGLU NM_000263.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.634
• Publications: 19 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: 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

ENSG00000266929 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-42537595-G-C is Benign according to our data. Variant chr17-42537595-G-C is described in ClinVar as Benign. ClinVar VariationId is 195051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGLU	NM_000263.4	MANE Select	c.531+50G>C		intron	N/A	NP_000254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGLU	ENST00000225927.7	TSL:1 MANE Select	c.531+50G>C		intron	N/A	ENSP00000225927.1
	NAGLU	ENST00000586516.5	TSL:2	c.133-744G>C		intron	N/A	ENSP00000467135.1
	NAGLU	ENST00000591587.1	TSL:5	c.127-744G>C		intron	N/A	ENSP00000467836.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113006 AN: 151938 Hom.: 42215 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.726

GnomAD2 exomes AF: 0.737 AC: 175008 AN: 237328 AF XY: 0.726

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.839

Gnomad ASJ exome AF: 0.822

Gnomad EAS exome AF: 0.732

Gnomad FIN exome AF: 0.714

Gnomad NFE exome AF: 0.737

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.728 AC: 1056631 AN: 1451666 Hom.: 386096 Cov.: 38 AF XY: 0.724 AC XY: 522611 AN XY: 722092

African (AFR) AF: 0.743 AC: 24753 AN: 33330

American (AMR) AF: 0.831 AC: 36705 AN: 44146

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 21470 AN: 26004

East Asian (EAS) AF: 0.741 AC: 29281 AN: 39516

South Asian (SAS) AF: 0.602 AC: 51552 AN: 85584

European-Finnish (FIN) AF: 0.712 AC: 34590 AN: 48574

Middle Eastern (MID) AF: 0.698 AC: 3379 AN: 4842

European-Non Finnish (NFE) AF: 0.731 AC: 811166 AN: 1109640

Other (OTH) AF: 0.729 AC: 43735 AN: 60030

GnomAD4 genome AF: 0.744 AC: 113090 AN: 152056 Hom.: 42250 Cov.: 32 AF XY: 0.741 AC XY: 55068 AN XY: 74312

African (AFR) AF: 0.750 AC: 31131 AN: 41496

American (AMR) AF: 0.798 AC: 12200 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2855 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3795 AN: 5144

South Asian (SAS) AF: 0.591 AC: 2850 AN: 4824

European-Finnish (FIN) AF: 0.714 AC: 7557 AN: 10584

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50265 AN: 67936

Other (OTH) AF: 0.721 AC: 1519 AN: 2106

Alfa AF: 0.763 Hom.: 8197

Bravo AF: 0.752

Asia WGS AF: 0.644 AC: 2238 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 08, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease axonal type 2V Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mucopolysaccharidosis, MPS-III-B Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2071046; hg19: chr17-40689613; COSMIC: COSV56794442; COSMIC: COSV56794442;