17-80220032-T-C

Position:

• chr17-80220032-T-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.32

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]

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]

ACMG classification

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	Protein	UniProt
SGSH	NM_000199.5	c.88+194A>G		intron_variant		ENST00000326317.11	NP_000190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11	c.88+194A>G		intron_variant		1	NM_000199.5	ENSP00000314606	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73837 AN: 151872 Hom.: 19390 Cov.: 32

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.: 3 AF XY: 0.400 AC XY: 72598 AN XY: 181416

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.: 32 AF XY: 0.488 AC XY: 36227 AN XY: 74284

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

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

Other links and lift over

dbSNP: rs4889841; hg19: chr17-78193831; COSMIC: COSV58338910; COSMIC: COSV58338910;