NM_000046.5:c.*2544_*2545dupTT

Variant names:

• chr5-78777851-C-CAA
• rs397976147
• NM_000046.5:c.*2544_*2545dupTT

Variant summary

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

The NM_000046.5(ARSB):​c.*2544_*2545dupTT 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 0.37 (5321 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARSB NM_000046.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5	c.*2544_*2545dupTT		3_prime_UTR_variant	Exon 8 of 8	ENST00000264914.10	NP_000037.2
ARSB	XM_011543390.2	c.*2544_*2545dupTT		3_prime_UTR_variant	Exon 9 of 9		XP_011541692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.*2544_*2545dupTT		3_prime_UTR_variant	Exon 8 of 8	1	NM_000046.5	ENSP00000264914.4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 31318 AN: 85324 Hom.: 5327 Cov.: 0

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.359

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.367 AC: 31299 AN: 85300 Hom.: 5321 Cov.: 0 AF XY: 0.364 AC XY: 14294 AN XY: 39262

African (AFR) AF: 0.470 AC: 9948 AN: 21182

American (AMR) AF: 0.316 AC: 2135 AN: 6754

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 824 AN: 2504

East Asian (EAS) AF: 0.475 AC: 1560 AN: 3286

South Asian (SAS) AF: 0.261 AC: 594 AN: 2276

European-Finnish (FIN) AF: 0.296 AC: 818 AN: 2768

Middle Eastern (MID) AF: 0.309 AC: 50 AN: 162

European-Non Finnish (NFE) AF: 0.331 AC: 14749 AN: 44606

Other (OTH) AF: 0.358 AC: 386 AN: 1078

Alfa AF: 0.00 Hom.: 0

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)

Splicing

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

Other links and lift over

dbSNP: rs397976147; hg19: chr5-78073674;