rs2071148

Positions:

• chr17-80210137-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000199.5(SGSH):​c.*315C>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 0.556 in 1,255,602 control chromosomes in the GnomAD database, including 198,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18626 hom., cov: 34)
  • Exomes 𝑓: 0.57 (179947 hom.)
• Consequence: SGSH NM_000199.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.351

Genes affected

SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

SGSH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-80210137-G-A is Benign according to our data. Variant chr17-80210137-G-A is described in ClinVar as [Benign]. Clinvar id is 325821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSH	NM_000199.5	c.*315C>T		3_prime_UTR_variant	8/8	ENST00000326317.11	NP_000190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317	c.*315C>T		3_prime_UTR_variant	8/8	1	NM_000199.5	ENSP00000314606.6

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72591 AN: 152062 Hom.: 18633 Cov.: 34

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.567 AC: 625947 AN: 1103420 Hom.: 179947 Cov.: 36 AF XY: 0.566 AC XY: 296565 AN XY: 524192

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.626

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.477 AC: 72593 AN: 152182 Hom.: 18626 Cov.: 34 AF XY: 0.477 AC XY: 35511 AN XY: 74400

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.479

Alfa AF: 0.529 Hom.: 7421

Bravo AF: 0.456

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071148; hg19: chr17-78183936;