17-80220203-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000199.5(SGSH):​c.88+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,488,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SGSH NM_000199.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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>T		intron	N/A	NP_000190.1	P51688
	SGSH	NM_001352921.3		c.88+23C>T		intron	N/A	NP_001339850.1
	SGSH	NM_001352922.2		c.88+23C>T		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>T		intron	N/A	ENSP00000314606.6	P51688
	SGSH	ENST00000575282.5	TSL:1	n.97+23C>T		intron	N/A
	SLC26A11	ENST00000945512.1		c.-14+215G>A		intron	N/A	ENSP00000615571.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000285 AC: 3 AN: 105142 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000477

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000512

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000292 AC: 39 AN: 1336862 Hom.: 0 Cov.: 28 AF XY: 0.0000258 AC XY: 17 AN XY: 659192

African (AFR) AF: 0.0000347 AC: 1 AN: 28794

American (AMR) AF: 0.0000604 AC: 2 AN: 33088

Ashkenazi Jewish (ASJ) AF: 0.0000419 AC: 1 AN: 23860

East Asian (EAS) AF: 0.00 AC: 0 AN: 33306

South Asian (SAS) AF: 0.0000531 AC: 4 AN: 75300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3996

European-Non Finnish (NFE) AF: 0.0000286 AC: 30 AN: 1049574

Other (OTH) AF: 0.0000179 AC: 1 AN: 55948

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74314

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Uncertain	0.98
PhyloP100		-0.26
PromoterAI		0.0052	Neutral

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;