17-42543794-C-T

Position:

chr17-42543794-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000263.4(NAGLU):c.1788C>T(p.Gly596Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,608,708 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 35 hom. )

Consequence

NAGLU
NM_000263.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 17-42543794-C-T is Benign according to our data. Variant chr17-42543794-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 281006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00464 (707/152334) while in subpopulation SAS AF= 0.00725 (35/4828). AF 95% confidence interval is 0.00672. There are 1 homozygotes in gnomad4. There are 320 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAGLU	NM_000263.4 linkuse as main transcript	c.1788C>T	p.Gly596Gly	synonymous_variant	6/6	ENST00000225927.7	NP_000254.2	P54802A0A140VJE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAGLU	ENST00000225927.7 linkuse as main transcript	c.1788C>T	p.Gly596Gly	synonymous_variant	6/6	1	NM_000263.4	ENSP00000225927.1	P54802
NAGLU	ENST00000591587.1 linkuse as main transcript	c.*757C>T		3_prime_UTR_variant	4/4	5		ENSP00000467836.1	K7EQH9
ENSG00000266929	ENST00000585572.1 linkuse as main transcript	n.379+5039C>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

707

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00554

AC:

1319

AN:

237968

Hom.:

AF XY:

0.00587

AC XY:

760

AN XY:

129442

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.00391

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00903

GnomAD4 exome

AF:

0.00617

AC:

8981

AN:

1456374

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

4624

AN XY:

724308

show subpopulations

Gnomad4 AFR exome

AF:

0.000868

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00766

Gnomad4 FIN exome

AF:

0.00495

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.00707

GnomAD4 genome

AF:

0.00464

AC:

707

AN:

152334

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.00725

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00632

Hom.:

Bravo

AF:

0.00432

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-B

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	NAGLU: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 19, 2016

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.1

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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