Variant chr17-80220203-G-C 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 NM_000199.5(SGSH):c.88+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 1,489,064 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 153 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 158 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.255

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:

SLC26A11 (HGNC:14471): (solute carrier family 26 member 11) This gene encodes a member of the solute linked carrier 26 family of anion exchangers. Members of this family of proteins are essential for numerous cellular functions including homeostasis and intracellular electrolyte balance. The encoded protein is a sodium independent sulfate transporter that is sensitive to the anion exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

SLC26A11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-80220203-G-C is Benign according to our data. Variant chr17-80220203-G-C is described in ClinVar as [Benign]. Clinvar id is 559108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 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.88+23C>G		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.88+23C>G		intron_variant		1	NM_000199.5	ENSP00000314606	P1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4033

AN:

152120

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.0205

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0115

AC:

1209

AN:

105142

Hom.:

AF XY:

0.0122

AC XY:

708

AN XY:

58078

show subpopulations

Gnomad AFR exome

AF:

0.0858

Gnomad AMR exome

AF:

0.00635

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.0167

Gnomad SAS exome

AF:

0.0222

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00432

GnomAD4 exome

AF:

0.00563

AC:

7529

AN:

1336826

Hom.:

158

Cov.:

AF XY:

0.00596

AC XY:

3930

AN XY:

659168

show subpopulations

Gnomad4 AFR exome

AF:

0.0878

Gnomad4 AMR exome

AF:

0.00768

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0227

Gnomad4 SAS exome

AF:

0.0216

Gnomad4 FIN exome

AF:

0.00291

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.0265

AC:

4036

AN:

152238

Hom.:

153

Cov.:

AF XY:

0.0262

AC XY:

1954

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0827

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.0205

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 08, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.5

DANN

Benign

0.82

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

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