chr17-80220032-T-C

Variant names:

• chr17-80220032-T-C
• rs4889841
• NM_000199.5:c.88+194A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SGSH	NM_000199.5	c.88+194A>G		intron_variant	Intron 1 of 7	ENST00000326317.11	NP_000190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSH	ENST00000326317.11	c.88+194A>G		intron_variant	Intron 1 of 7	1	NM_000199.5	ENSP00000314606.6

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

African (AFR) AF: 0.682 AC: 5143 AN: 7544

American (AMR) AF: 0.565 AC: 5446 AN: 9642

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 4128 AN: 10896

East Asian (EAS) AF: 0.309 AC: 7227 AN: 23396

South Asian (SAS) AF: 0.469 AC: 13742 AN: 29284

European-Finnish (FIN) AF: 0.410 AC: 11225 AN: 27346

Middle Eastern (MID) AF: 0.430 AC: 703 AN: 1634

European-Non Finnish (NFE) AF: 0.376 AC: 80476 AN: 213954

Other (OTH) AF: 0.430 AC: 8976 AN: 20894

GnomAD4 genome AF: 0.487 AC: 73948 AN: 151990 Hom.: 19437 Cov.: 32 AF XY: 0.488 AC XY: 36227 AN XY: 74284

African (AFR) AF: 0.686 AC: 28420 AN: 41452

American (AMR) AF: 0.544 AC: 8311 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2000 AN: 5138

South Asian (SAS) AF: 0.491 AC: 2364 AN: 4818

European-Finnish (FIN) AF: 0.415 AC: 4389 AN: 10574

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25638 AN: 67946

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.418 Hom.: 20349

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.72
PhyloP100		-3.3
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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