rs968875282

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000263.4(NAGLU):c.7G>T(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,065,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

NAGLU
NM_000263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.479

Publications

0 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: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Orphanet, G2P, Myriad Women’s Health
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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2001935).

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.7G>T	p.Ala3Ser	missense	Exon 1 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.7G>T	p.Ala3Ser	missense	Exon 1 of 6	ENSP00000225927.1	P54802
NAGLU	ENST00000963429.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 6	ENSP00000633488.1
NAGLU	ENST00000904921.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 7	ENSP00000574980.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000188

AC:

AN:

1065882

Hom.:

Cov.:

AF XY:

0.00000397

AC XY:

AN XY:

503388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22292

American (AMR)

AF:

0.00

AC:

AN:

7912

Ashkenazi Jewish (ASJ)

AF:

0.000146

AC:

AN:

13654

East Asian (EAS)

AF:

0.00

AC:

AN:

25308

South Asian (SAS)

AF:

0.00

AC:

AN:

19416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2826

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

911118

Other (OTH)

AF:

0.00

AC:

AN:

42632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.17

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

1.6

PhyloP100

0.48

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.23

REVEL

Benign

0.28

Sift

Benign

0.054

Sift4G

Benign

0.21

Polyphen

0.043

Vest4

0.23

MutPred

0.23

Gain of glycosylation at A3 (P = 0.03)

MVP

0.74

MPC

0.33

ClinPred

0.20

GERP RS

2.3

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.057

gMVP

0.44

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over