NM_000263.4:c.1860C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000263.4(NAGLU):c.1860C>T(p.Ser620Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,603,066 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 12 hom. )

Consequence

NAGLU
NM_000263.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.476

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 17-42543866-C-T is Benign according to our data. Variant chr17-42543866-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 323304.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}. Variant chr17-42543866-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.476 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00175 (267/152344) while in subpopulation NFE AF= 0.00341 (232/68028). AF 95% confidence interval is 0.00305. There are 1 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAGLU	NM_000263.4 link	c.1860C>T	p.Ser620Ser	synonymous_variant	Exon 6 of 6	ENST00000225927.7	NP_000254.2	P54802A0A140VJE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAGLU	ENST00000225927.7 link	c.1860C>T	p.Ser620Ser	synonymous_variant	Exon 6 of 6	1	NM_000263.4	ENSP00000225927.1	P54802
NAGLU	ENST00000591587.1 link	c.*829C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000467836.1	K7EQH9
ENSG00000266929	ENST00000585572.1 link	n.379+5111C>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00168

AC:

381

AN:

227436

Hom.:

AF XY:

0.00161

AC XY:

199

AN XY:

123676

show subpopulations

Gnomad AFR exome

AF:

0.000361

Gnomad AMR exome

AF:

0.000466

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000576

Gnomad NFE exome

AF:

0.00323

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00316

AC:

4584

AN:

1450722

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2186

AN XY:

720864

show subpopulations

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.000513

Gnomad4 ASJ exome

AF:

0.000775

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00304

GnomAD4 genome

AF:

0.00175

AC:

267

AN:

152344

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00164

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-B

Uncertain:1Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NAGLU: BP4, BP7 -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.8

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over