rs77032342

Variant names:

• chr17-80220203-G-C
• rs77032342
• NM_000199.5:c.88+23C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-80220203-G-C
• chr17-80220203-G-A
• chr17-80220203-G-T

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+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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.255
• Publications: 2 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=-0.78).
• BP6: Variant 17-80220203-G-C is Benign according to our data. Variant chr17-80220203-G-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000199.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSH	NM_000199.5	MANE Select	c.88+23C>G		intron	N/A	NP_000190.1	P51688
	SGSH	NM_001352921.3		c.88+23C>G		intron	N/A	NP_001339850.1
	SGSH	NM_001352922.2		c.88+23C>G		intron	N/A	NP_001339851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSH	ENST00000326317.11	TSL:1 MANE Select	c.88+23C>G		intron	N/A	ENSP00000314606.6	P51688
	SGSH	ENST00000575282.5	TSL:1	n.97+23C>G		intron	N/A
	SLC26A11	ENST00000945512.1		c.-14+215G>C		intron	N/A	ENSP00000615571.1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4033 AN: 152120 Hom.: 154 Cov.: 33

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

GnomAD2 exomes AF: 0.0115 AC: 1209 AN: 105142 AF XY: 0.0122

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 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.: 28 AF XY: 0.00596 AC XY: 3930 AN XY: 659168

African (AFR) AF: 0.0878 AC: 2528 AN: 28782

American (AMR) AF: 0.00768 AC: 254 AN: 33082

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 376 AN: 23858

East Asian (EAS) AF: 0.0227 AC: 757 AN: 33306

South Asian (SAS) AF: 0.0216 AC: 1629 AN: 75292

European-Finnish (FIN) AF: 0.00291 AC: 96 AN: 32994

Middle Eastern (MID) AF: 0.0160 AC: 64 AN: 3996

European-Non Finnish (NFE) AF: 0.00115 AC: 1208 AN: 1049570

Other (OTH) AF: 0.0110 AC: 617 AN: 55946

GnomAD4 genome AF: 0.0265 AC: 4036 AN: 152238 Hom.: 153 Cov.: 33 AF XY: 0.0262 AC XY: 1954 AN XY: 74442

African (AFR) AF: 0.0827 AC: 3437 AN: 41548

American (AMR) AF: 0.0104 AC: 159 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3466

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5170

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4814

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 67998

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.00356 Hom.: 3

Bravo AF: 0.0289

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.82
PhyloP100		-0.26
PromoterAI		-0.048	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: rs77032342; hg19: chr17-78194002;