NM_000046.5:c.*2975G>T

Variant names:

• chr5-78777422-C-A
• rs3088247
• NM_000046.5:c.*2975G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000046.5(ARSB):​c.*2975G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,444 control chromosomes in the GnomAD database, including 49,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49090 hom., cov: 31)
  • Exomes 𝑓: 0.75 (120 hom.)
• Consequence: ARSB NM_000046.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.206
• Publications: 5 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, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Illumina, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-78777422-C-A is Benign according to our data. Variant chr5-78777422-C-A is described in ClinVar as Benign. ClinVar VariationId is 354262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000046.5. 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
	ARSB	NM_000046.5	MANE Select	c.*2975G>T		3_prime_UTR	Exon 8 of 8	NP_000037.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.*2975G>T		3_prime_UTR	Exon 8 of 8	ENSP00000264914.4	P15848-1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121027 AN: 151894 Hom.: 49043 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.745 AC: 322 AN: 432 Hom.: 120 Cov.: 0 AF XY: 0.746 AC XY: 194 AN XY: 260

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) AF: 0.742 AC: 316 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.797 AC: 121122 AN: 152012 Hom.: 49090 Cov.: 31 AF XY: 0.791 AC XY: 58764 AN XY: 74284

African (AFR) AF: 0.940 AC: 38994 AN: 41482

American (AMR) AF: 0.784 AC: 11969 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2851 AN: 3472

East Asian (EAS) AF: 0.581 AC: 3001 AN: 5168

South Asian (SAS) AF: 0.561 AC: 2700 AN: 4812

European-Finnish (FIN) AF: 0.738 AC: 7781 AN: 10538

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51387 AN: 67960

Other (OTH) AF: 0.765 AC: 1614 AN: 2110

Alfa AF: 0.765 Hom.: 22773

Bravo AF: 0.808

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis type 6 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.21
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3088247; hg19: chr5-78073245; COSMIC: COSV53722226; COSMIC: COSV53722226;