rs1802465661

Variant names:

• chr8-43140390-C-A
• rs1802465661
• NM_152419.3:c.-107C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-43140390-C-A
• chr8-43140390-C-T

Variant summary

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

The NM_152419.3(HGSNAT):​c.-107C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 331,558 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: HGSNAT NM_152419.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

Genes affected

HGSNAT (HGNC:26527): (heparan-alpha-glucosaminide N-acetyltransferase) This gene encodes a lysosomal acetyltransferase, which is one of several enzymes involved in the lysosomal degradation of heparin sulfate. Mutations in this gene are associated with Sanfilippo syndrome C, one type of the lysosomal storage disease mucopolysaccaridosis III, which results from impaired degradation of heparan sulfate. [provided by RefSeq, Jan 2009]

HGSNAT Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 3

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• mucopolysaccharidosis type 3C

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics, G2P
• retinitis pigmentosa 73

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGSNAT	NM_152419.3	c.-107C>A		upstream_gene_variant		ENST00000379644.9	NP_689632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGSNAT	ENST00000379644.9	c.-107C>A		upstream_gene_variant		2	NM_152419.3	ENSP00000368965.4
HGSNAT	ENST00000520704.1	n.-257C>A		upstream_gene_variant		1		ENSP00000429109.1
HGSNAT	ENST00000517319.1	n.-107C>A		upstream_gene_variant		4		ENSP00000430032.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000302 AC: 1 AN: 331558 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 155864

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

African (AFR) AF: 0.00 AC: 0 AN: 6188

American (AMR) AF: 0.00 AC: 0 AN: 438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2076

East Asian (EAS) AF: 0.00 AC: 0 AN: 1380

South Asian (SAS) AF: 0.00 AC: 0 AN: 7090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 686

European-Non Finnish (NFE) AF: 0.00000330 AC: 1 AN: 302734

Other (OTH) AF: 0.00 AC: 0 AN: 10796

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		2.7
PromoterAI		0.16	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1802465661; hg19: chr8-42995533;