Variant 17-42537595-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.634

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NAGLU	NM_000263.4 linkuse as main transcript	c.531+50G>C	intron_variant	ENST00000225927.7
NAGLU	XM_024450771.2 linkuse as main transcript	c.588+50G>C	intron_variant
NAGLU	XM_047436138.1 linkuse as main transcript	c.-78-744G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
NAGLU	ENST00000225927.7 linkuse as main transcript	c.531+50G>C	intron_variant	1	NM_000263.4	P1
NAGLU	ENST00000586516.5 linkuse as main transcript	c.134-744G>C	intron_variant	2
NAGLU	ENST00000590358.1 linkuse as main transcript	c.219+50G>C	intron_variant	4
NAGLU	ENST00000591587.1 linkuse as main transcript	c.127-744G>C	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113006

AN:

151938

Hom.:

42215

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.737

AC:

175008

AN:

237328

Hom.:

64983

AF XY:

0.726

AC XY:

93863

AN XY:

129290

show subpopulations

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 SAS exome

AF:

0.603

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.:

AF XY:

0.724

AC XY:

522611

AN XY:

722092

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.831

Gnomad4 ASJ exome

AF:

0.826

Gnomad4 EAS exome

AF:

0.741

Gnomad4 SAS exome

AF:

0.602

Gnomad4 FIN exome

AF:

0.712

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.744

AC:

113090

AN:

152056

Hom.:

42250

Cov.:

AF XY:

0.741

AC XY:

55068

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.798

Gnomad4 ASJ

AF:

0.823

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.714

Gnomad4 NFE

AF:

0.740

Gnomad4 OTH

AF:

0.721

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 08, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Charcot-Marie-Tooth disease axonal type 2V

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Mucopolysaccharidosis, MPS-III-B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.8

DANN

Benign

0.34

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