rs9900509

chr17-80217237-C-T

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.89-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,571,782 control chromosomes in the GnomAD database, including 4,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1883 hom., cov: 34)
  • Exomes 𝑓: 0.044 (2692 hom.)
• Consequence: SGSH NM_000199.5 intron
• Scores: Splicing: ADA: 0.00002686
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.197

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-80217237-C-T is Benign according to our data. Variant chr17-80217237-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSH	NM_000199.5	c.89-45G>A		intron_variant		ENST00000326317.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSH	ENST00000326317.11	c.89-45G>A		intron_variant		1	NM_000199.5	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16612 AN: 152086 Hom.: 1879 Cov.: 34

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0893

GnomAD3 exomes AF: 0.0600 AC: 11223 AN: 187028 Hom.: 746 AF XY: 0.0569 AC XY: 5736 AN XY: 100780

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.0367

Gnomad ASJ exome AF: 0.0616

Gnomad EAS exome AF: 0.0108

Gnomad SAS exome AF: 0.0591

Gnomad FIN exome AF: 0.0643

Gnomad NFE exome AF: 0.0399

Gnomad OTH exome AF: 0.0527

GnomAD4 exome AF: 0.0437 AC: 62082 AN: 1419578 Hom.: 2692 Cov.: 30 AF XY: 0.0435 AC XY: 30584 AN XY: 703624

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.0388

Gnomad4 ASJ exome AF: 0.0612

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.0633

Gnomad4 NFE exome AF: 0.0338

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.109 AC: 16647 AN: 152204 Hom.: 1883 Cov.: 34 AF XY: 0.109 AC XY: 8087 AN XY: 74436

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0898

Alfa AF: 0.0700 Hom.: 162

Bravo AF: 0.117

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Mucopolysaccharidosis, MPS-III-A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.1
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.070		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: rs9900509; hg19: chr17-78191036;