chr17-80220230-G-T

Variant names:

• chr17-80220230-G-T
• rs1219782774
• NM_000199.5:c.84C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000199.5(SGSH):​c.84C>A​(p.Leu28Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L28L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGSH NM_000199.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100
• Publications: 0 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-80220230-G-T is Benign according to our data. Variant chr17-80220230-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1615254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.1 with no splicing effect.

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.84C>A	p.Leu28Leu	synonymous	Exon 1 of 8	NP_000190.1	P51688
	SGSH	NM_001352921.3		c.84C>A	p.Leu28Leu	synonymous	Exon 1 of 8	NP_001339850.1
	SGSH	NM_001352922.2		c.84C>A	p.Leu28Leu	synonymous	Exon 1 of 9	NP_001339851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSH	ENST00000326317.11	TSL:1 MANE Select	c.84C>A	p.Leu28Leu	synonymous	Exon 1 of 8	ENSP00000314606.6	P51688
	SGSH	ENST00000575282.5	TSL:1	n.93C>A		non_coding_transcript_exon	Exon 1 of 5
	SGSH	ENST00000874335.1		c.84C>A	p.Leu28Leu	synonymous	Exon 1 of 9	ENSP00000544394.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1367928 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 674706

African (AFR) AF: 0.00 AC: 0 AN: 29772

American (AMR) AF: 0.00 AC: 0 AN: 34768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24720

East Asian (EAS) AF: 0.00 AC: 0 AN: 34158

South Asian (SAS) AF: 0.00 AC: 0 AN: 77632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072316

Other (OTH) AF: 0.00 AC: 0 AN: 57180

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis, MPS-III-A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.7
DANN	Benign	0.94
PhyloP100		0.10
PromoterAI		0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs1219782774; hg19: chr17-78194029;