rs201168448

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_000046.5(ARSB):c.98C>T(p.Ala33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,453,254 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A33A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0098 ( 19 hom., cov: 33)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

ARSB
NM_000046.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.567

Publications

6 publications found

Variant links:

Genes affected

ARSB (HGNC:714): (arylsulfatase B) Arylsulfatase B encoded by this gene belongs to the sulfatase family. The arylsulfatase B homodimer hydrolyzes sulfate groups of N-Acetyl-D-galactosamine, chondriotin sulfate, and dermatan sulfate. The protein is targeted to the lysozyme. Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2016]

ARSB Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ARSB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 85 curated pathogenic missense variants (we use a threshold of 10). The gene has 14 curated benign missense variants. Gene score misZ: 0.63089 (below the threshold of 3.09). Trascript score misZ: -0.06109 (below the threshold of 3.09). GenCC associations: The gene is linked to mucopolysaccharidosis type 6.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036388934).

BP6

Variant 5-78985151-G-A is Benign according to our data. Variant chr5-78985151-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00982 (1488/151474) while in subpopulation AMR AF = 0.012 (183/15246). AF 95% confidence interval is 0.0111. There are 19 homozygotes in GnomAd4. There are 820 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5 link	c.98C>T	p.Ala33Val	missense_variant	Exon 1 of 8	ENST00000264914.10	NP_000037.2	P15848-1A0A024RAJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSB	ENST00000264914.10 link	c.98C>T	p.Ala33Val	missense_variant	Exon 1 of 8	1	NM_000046.5	ENSP00000264914.4	P15848-1
ARSB	ENST00000396151.7 link	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 8	1		ENSP00000379455.3	P15848-2
ARSB	ENST00000565165.2 link	c.98C>T	p.Ala33Val	missense_variant	Exon 1 of 5	1		ENSP00000456339.2	A0A2U3U034
ARSB	ENST00000521117.1 link	c.98C>T	p.Ala33Val	missense_variant	Exon 2 of 2	3		ENSP00000428611.1	E5RHC4

Frequencies

GnomAD3 genomes

AF:

0.00984

AC:

1489

AN:

151366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00233

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0344

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00480

GnomAD2 exomes

AF:

0.0105

AC:

1087

AN:

103530

AF XY:

0.00991

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00418

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0336

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00921

GnomAD4 exome

AF:

0.0124

AC:

16196

AN:

1301780

Hom.:

130

Cov.:

AF XY:

0.0120

AC XY:

7676

AN XY:

640686

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

27046

American (AMR)

AF:

0.00522

AC:

131

AN:

25084

Ashkenazi Jewish (ASJ)

AF:

0.00983

AC:

213

AN:

21660

East Asian (EAS)

AF:

0.0000337

AC:

AN:

29704

South Asian (SAS)

AF:

0.000258

AC:

AN:

65912

European-Finnish (FIN)

AF:

0.0287

AC:

1168

AN:

40698

Middle Eastern (MID)

AF:

0.000900

AC:

AN:

4444

European-Non Finnish (NFE)

AF:

0.0135

AC:

13978

AN:

1034166

Other (OTH)

AF:

0.0121

AC:

643

AN:

53066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1064

2129

3193

4258

5322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.00982

AC:

1488

AN:

151474

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

820

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.00232

AC:

AN:

41356

American (AMR)

AF:

0.0120

AC:

183

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00981

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.000624

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0344

AC:

358

AN:

10416

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0118

AC:

798

AN:

67748

Other (OTH)

AF:

0.00475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0102

Hom.:

Bravo

AF:

0.00852

ESP6500AA

AF:

0.00457

AC:

ESP6500EA

AF:

0.0111

AC:

ExAC

AF:

0.00757

AC:

822

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis type 6

Benign:6

Oct 30, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 01, 2018

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

Allele frequency greater than expected for disorder (BS1); Homozygotes reported in GnomAD (BS2); Classified benign by a reputable source (BP6) -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:4

Jun 16, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARSB: BS1, BS2 -

Nov 03, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17458871, 21228398, 22133300) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 19, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ARSB-related disorder

Benign:1

Mar 23, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Benign

4.4

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.32

T;.;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.33

T;T;T;T

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.34

N;N;.;.

PhyloP100

-0.57

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.39

N;N;N;D

REVEL

Uncertain

0.35

Sift

Benign

0.76

T;T;T;.

Sift4G

Benign

0.31

T;T;T;.

Polyphen

0.0020

B;.;.;.

Vest4

0.54

MPC

1.5

ClinPred

0.0025

GERP RS

-1.4

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.026

gMVP

0.55

Mutation Taster

=95/5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over