Variant rs9900509 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000326317.11(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
ENST00000326317.11 intron

Scores

Splicing: ADA: 0.00002686

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.197

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SGSH	NM_000199.5 linkuse as main transcript	c.89-45G>A		intron_variant		ENST00000326317.11	NP_000190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11 linkuse as main transcript	c.89-45G>A		intron_variant		1	NM_000199.5	ENSP00000314606	P1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16612

AN:

152086

Hom.:

1879

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0435

AC XY:

30584

AN XY:

703624

show subpopulations

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.:

AF XY:

0.109

AC XY:

8087

AN XY:

74436

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over