rs1802478718

Variant names:

• chr8-43140524-G-A
• rs1802478718
• NM_152419.3:c.28G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-43140524-G-A
• chr8-43140524-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152419.3(HGSNAT):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 952,324 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HGSNAT NM_152419.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• 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):

• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10419813).

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.28G>A	p.Ala10Thr	missense	Exon 1 of 18	NP_689632.2
	HGSNAT	NM_001363227.2		c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	NP_001350156.1
	HGSNAT	NM_001363228.2		c.28G>A	p.Ala10Thr	missense	Exon 1 of 16	NP_001350157.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGSNAT	ENST00000379644.9	TSL:2 MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 18	ENSP00000368965.4	Q68CP4-2
	HGSNAT	ENST00000520704.1	TSL:1	n.-123G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000429109.1	E5RJC4
	HGSNAT	ENST00000520704.1	TSL:1	n.-123G>A		5_prime_UTR	Exon 1 of 10	ENSP00000429109.1	E5RJC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 2 AN: 952324 Hom.: 0 Cov.: 29 AF XY: 0.00000223 AC XY: 1 AN XY: 448804

African (AFR) AF: 0.00 AC: 0 AN: 18616

American (AMR) AF: 0.00 AC: 0 AN: 4282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8954

East Asian (EAS) AF: 0.00 AC: 0 AN: 13552

South Asian (SAS) AF: 0.00 AC: 0 AN: 18736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2240

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839916

Other (OTH) AF: 0.00 AC: 0 AN: 34546

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.63	T
PhyloP100		-0.25
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.20
Sift	Benign	0.20	T
Sift4G	Benign	0.41	T
Vest4		0.082
MVP		0.56
MPC		0.098
ClinPred		0.13	T
GERP RS		0.93
PromoterAI		-0.083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.40
Mutation Taster		=94/6	polymorphism

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: rs1802478718; hg19: chr8-42995667;