5-78984985-C-T

Variant names:

• chr5-78984985-C-T
• rs750947605
• NM_000046.5:c.264G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_000046.5(ARSB):​c.264G>A​(p.Gln88Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000146 in 1,372,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ARSB NM_000046.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.76
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 5-78984985-C-T is Benign according to our data. Variant chr5-78984985-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1095806.Status of the report is criteria_provided_single_submitter, 1 stars.

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.264G>A	p.Gln88Gln	synonymous	Exon 1 of 8	NP_000037.2
	ARSB	NM_198709.3		c.264G>A	p.Gln88Gln	synonymous	Exon 2 of 8	NP_942002.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.264G>A	p.Gln88Gln	synonymous	Exon 1 of 8	ENSP00000264914.4
	ARSB	ENST00000396151.7	TSL:1	c.264G>A	p.Gln88Gln	synonymous	Exon 2 of 8	ENSP00000379455.3
	ARSB	ENST00000565165.2	TSL:1	c.264G>A	p.Gln88Gln	synonymous	Exon 1 of 5	ENSP00000456339.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000589 AC: 1 AN: 169770 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000129

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1372674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681968

African (AFR) AF: 0.00 AC: 0 AN: 28542

American (AMR) AF: 0.00 AC: 0 AN: 34432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23882

East Asian (EAS) AF: 0.00 AC: 0 AN: 31630

South Asian (SAS) AF: 0.00 AC: 0 AN: 76088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4572

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070460

Other (OTH) AF: 0.00 AC: 0 AN: 55978

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis type 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		5.8
PromoterAI		-0.016	Neutral

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: rs750947605; hg19: chr5-78280808;