rs16876029

Variant names:

• chr5-78885658-T-A
• rs16876029
• NM_000046.5:c.1068A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-78885658-T-A
• chr5-78885658-T-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000046.5(ARSB):​c.1068A>T​(p.Thr356Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,613,994 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (30 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (20 hom.)
• Consequence: ARSB NM_000046.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.47
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-78885658-T-A is Benign according to our data. Variant chr5-78885658-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 527328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.47 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00878 (1335/152104) while in subpopulation AFR AF = 0.0308 (1277/41482). AF 95% confidence interval is 0.0294. There are 30 homozygotes in GnomAd4. There are 600 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	NM_000046.5	MANE Select	c.1068A>T	p.Thr356Thr	synonymous	Exon 5 of 8	NP_000037.2
	ARSB	NM_198709.3		c.1068A>T	p.Thr356Thr	synonymous	Exon 6 of 8	NP_942002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.1068A>T	p.Thr356Thr	synonymous	Exon 5 of 8	ENSP00000264914.4
	ARSB	ENST00000396151.7	TSL:1	c.1068A>T	p.Thr356Thr	synonymous	Exon 6 of 8	ENSP00000379455.3
	ARSB	ENST00000565165.2	TSL:1	c.1068A>T	p.Thr356Thr	synonymous	Exon 5 of 5	ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.00872 AC: 1326 AN: 151986 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00625

GnomAD2 exomes AF: 0.00234 AC: 587 AN: 251218 AF XY: 0.00172

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.000935 AC: 1367 AN: 1461890 Hom.: 20 Cov.: 35 AF XY: 0.000769 AC XY: 559 AN XY: 727246

African (AFR) AF: 0.0315 AC: 1054 AN: 33480

American (AMR) AF: 0.00250 AC: 112 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1112010

Other (OTH) AF: 0.00212 AC: 128 AN: 60396

GnomAD4 genome AF: 0.00878 AC: 1335 AN: 152104 Hom.: 30 Cov.: 32 AF XY: 0.00807 AC XY: 600 AN XY: 74360

African (AFR) AF: 0.0308 AC: 1277 AN: 41482

American (AMR) AF: 0.00262 AC: 40 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00618 AC: 13 AN: 2102

Alfa AF: 0.00234 Hom.: 1

Bravo AF: 0.00948

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Mucopolysaccharidosis type 6 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.25
DANN	Benign	0.64
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs16876029; hg19: chr5-78181481;