rs2144831422

Variant names:

• chr17-80220212-G-A
• rs2144831422
• NM_000199.5:c.88+14C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000199.5(SGSH):​c.88+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SGSH NM_000199.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.127
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-80220212-G-A is Benign according to our data. Variant chr17-80220212-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1626081.Status of the report is criteria_provided_single_submitter, 1 stars.

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+14C>T		intron	N/A	NP_000190.1	P51688
	SGSH	NM_001352921.3		c.88+14C>T		intron	N/A	NP_001339850.1
	SGSH	NM_001352922.2		c.88+14C>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+14C>T		intron	N/A	ENSP00000314606.6	P51688
	SGSH	ENST00000575282.5	TSL:1	n.97+14C>T		intron	N/A
	SLC26A11	ENST00000945512.1		c.-14+224G>A		intron	N/A	ENSP00000615571.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358242 Hom.: 0 Cov.: 29 AF XY: 0.00000149 AC XY: 1 AN XY: 669866

African (AFR) AF: 0.00 AC: 0 AN: 29396

American (AMR) AF: 0.0000294 AC: 1 AN: 34040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24408

East Asian (EAS) AF: 0.00 AC: 0 AN: 33792

South Asian (SAS) AF: 0.00 AC: 0 AN: 76790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065768

Other (OTH) AF: 0.00 AC: 0 AN: 56810

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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	-0.72
CADD	Benign	7.8
DANN	Uncertain	0.98
PhyloP100		0.13
PromoterAI		0.084	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: rs2144831422; hg19: chr17-78194011;