chr5-78777851-C-CAAA

Position:

• chr5-78777851-C-CAAA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_000046.5(ARSB):​c.*2545_*2546insTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.016 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARSB NM_000046.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.633

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0159 (1360/85362) while in subpopulation AFR AF= 0.0301 (636/21156). AF 95% confidence interval is 0.0281. There are 24 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.*2545_*2546insTTT		3_prime_UTR_variant	8/8	ENST00000264914.10
ARSB	XM_011543390.2	c.*2545_*2546insTTT		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.*2545_*2546insTTT		3_prime_UTR_variant	8/8	1	NM_000046.5	P1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 1360 AN: 85384 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.0487

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00514

Gnomad SAS AF: 0.00261

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.00562

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0112

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

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0159 AC: 1360 AN: 85362 Hom.: 24 Cov.: 0 AF XY: 0.0151 AC XY: 594 AN XY: 39298

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.00515

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.00360

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0111

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis type 6 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397976147; hg19: chr5-78073674;