17-42543794-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. G596G) has been classified 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

Publications

3 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: Genomics England PanelApp, Myriad Women’s Health, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
Charcot-Marie-Tooth disease axonal type 2V
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

NAGLU links:

ENSG00000266929 (HGNC:):

ENSG00000266929 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 35 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGLU	NM_000263.4	MANE Select	c.1788C>T	p.Gly596Gly	synonymous	Exon 6 of 6	NP_000254.2	A0A140VJE4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAGLU	ENST00000225927.7	TSL:1 MANE Select	c.1788C>T	p.Gly596Gly	synonymous	Exon 6 of 6	ENSP00000225927.1	P54802
NAGLU	ENST00000963429.1		c.1866C>T	p.Gly622Gly	synonymous	Exon 6 of 6	ENSP00000633488.1
NAGLU	ENST00000904921.1		c.1845C>T	p.Gly615Gly	synonymous	Exon 7 of 7	ENSP00000574980.1

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

GnomAD2 exomes

AF:

0.00554

AC:

1319

AN:

237968

AF XY:

0.00587

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 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

African (AFR)

AF:

0.000868

AC:

AN:

33396

American (AMR)

AF:

0.00293

AC:

129

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

380

AN:

25986

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39532

South Asian (SAS)

AF:

0.00766

AC:

656

AN:

85666

European-Finnish (FIN)

AF:

0.00495

AC:

254

AN:

51352

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5762

European-Non Finnish (NFE)

AF:

0.00631

AC:

7001

AN:

1110378

Other (OTH)

AF:

0.00707

AC:

426

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

662

1324

1986

2648

3310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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

AF:

0.00464

AC:

707

AN:

152334

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41584

American (AMR)

AF:

0.00170

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00330

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00725

AC:

493

AN:

68026

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00632

Hom.:

Bravo

AF:

0.00432

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mucopolysaccharidosis, MPS-III-B (2)

not provided (2)

Mucopolysaccharidosis, MPS-III-B;C5569050:Charcot-Marie-Tooth disease axonal type 2V (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.1

(source)

DANN

Benign

0.63

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over