Variant chr17-80220032-T-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+194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 496,580 control chromosomes in the GnomAD database, including 47,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19437 hom., cov: 32)

Exomes 𝑓: 0.40 ( 28376 hom. )

Consequence

SGSH
NM_000199.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.32

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=-0.87).

BP6

Variant 17-80220032-T-C is Benign according to our data. Variant chr17-80220032-T-C is described in ClinVar as [Benign]. Clinvar id is 1295737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSH	NM_000199.5 linkuse as main transcript	c.88+194A>G		intron_variant		ENST00000326317.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSH	ENST00000326317.11 linkuse as main transcript	c.88+194A>G		intron_variant		1	NM_000199.5	P1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73837

AN:

151872

Hom.:

19390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.488

GnomAD4 exome

AF:

0.398

AC:

137066

AN:

344590

Hom.:

28376

Cov.:

AF XY:

0.400

AC XY:

72598

AN XY:

181416

show subpopulations

Gnomad4 AFR exome

AF:

0.682

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.487

AC:

73948

AN:

151990

Hom.:

19437

Cov.:

AF XY:

0.488

AC XY:

36227

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.686

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.379

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.415

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.406

Hom.:

14970

Bravo

AF:

0.508

Asia WGS

AF:

0.471

AC:

1638

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.72

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