rs72647302

Variant names:

• chr8-43159090-G-T
• rs72647302
• NM_152419.3:c.493+46G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152419.3(HGSNAT):​c.493+46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,586,514 control chromosomes in the GnomAD database, including 2,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (115 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1945 hom.)
• Consequence: HGSNAT NM_152419.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23
• Publications: 2 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):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mucopolysaccharidosis type 3

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

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-43159090-G-T is Benign according to our data. Variant chr8-43159090-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152419.3. 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
	HGSNAT	NM_152419.3	MANE Select	c.493+46G>T		intron	N/A	NP_689632.2
	HGSNAT	NM_001363227.2		c.493+46G>T		intron	N/A	NP_001350156.1
	HGSNAT	NM_001363228.2		c.493+46G>T		intron	N/A	NP_001350157.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGSNAT	ENST00000379644.9	TSL:2 MANE Select	c.493+46G>T		intron	N/A	ENSP00000368965.4	Q68CP4-2
	HGSNAT	ENST00000520704.1	TSL:1	n.343+46G>T		intron	N/A	ENSP00000429109.1	E5RJC4
	HGSNAT	ENST00000902460.1		c.493+46G>T		intron	N/A	ENSP00000572519.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5032 AN: 152022 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.00964

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0324 AC: 7662 AN: 236598 AF XY: 0.0327

Gnomad AFR exome AF: 0.00867

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.000404

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0488

Gnomad OTH exome AF: 0.0414

GnomAD4 exome AF: 0.0483 AC: 69335 AN: 1434374 Hom.: 1945 Cov.: 29 AF XY: 0.0476 AC XY: 33815 AN XY: 710990

African (AFR) AF: 0.00750 AC: 244 AN: 32532

American (AMR) AF: 0.0277 AC: 1153 AN: 41584

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 516 AN: 25578

East Asian (EAS) AF: 0.00128 AC: 50 AN: 38998

South Asian (SAS) AF: 0.0134 AC: 1102 AN: 81966

European-Finnish (FIN) AF: 0.0308 AC: 1623 AN: 52692

Middle Eastern (MID) AF: 0.0127 AC: 72 AN: 5664

European-Non Finnish (NFE) AF: 0.0566 AC: 62064 AN: 1096290

Other (OTH) AF: 0.0425 AC: 2511 AN: 59070

GnomAD4 genome AF: 0.0331 AC: 5032 AN: 152140 Hom.: 115 Cov.: 32 AF XY: 0.0313 AC XY: 2328 AN XY: 74382

African (AFR) AF: 0.00961 AC: 399 AN: 41524

American (AMR) AF: 0.0372 AC: 568 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4816

European-Finnish (FIN) AF: 0.0313 AC: 331 AN: 10580

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3511 AN: 67990

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0451 Hom.: 75

Bravo AF: 0.0330

Asia WGS AF: 0.00693 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.54
PhyloP100		-1.2
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: rs72647302; hg19: chr8-43014233;