Genetic Variant NM_000046.5:c.*2545dupT (chr5-78777851-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000046.5(ARSB):c.*2545dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 1511 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARSB
NM_000046.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

Publications

1 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5 link	c.*2545dupT		3_prime_UTR_variant	Exon 8 of 8	ENST00000264914.10	NP_000037.2	P15848-1A0A024RAJ9
ARSB	XM_011543390.2 link	c.*2545dupT		3_prime_UTR_variant	Exon 9 of 9		XP_011541692.1	P15848-1A0A024RAJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10 link	c.*2545dupT		3_prime_UTR_variant	Exon 8 of 8	1	NM_000046.5	ENSP00000264914.4		P15848-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

14980

AN:

85412

Hom.:

1509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0963

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.175

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.175

AC:

14979

AN:

85390

Hom.:

1511

Cov.:

AF XY:

0.170

AC XY:

6683

AN XY:

39302

show subpopulations

African (AFR)

AF:

0.0964

AC:

2049

AN:

21264

American (AMR)

AF:

0.145

AC:

980

AN:

6756

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

681

AN:

2504

East Asian (EAS)

AF:

0.0745

AC:

246

AN:

3300

South Asian (SAS)

AF:

0.194

AC:

442

AN:

2282

European-Finnish (FIN)

AF:

0.146

AC:

405

AN:

2778

Middle Eastern (MID)

AF:

0.302

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.219

AC:

9760

AN:

44578

Other (OTH)

AF:

0.178

AC:

193

AN:

1082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

581

1162

1743

2324

2905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_000046.5:c.*2545dupT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over