NM_152419.3:c.14G>A

Variant names:

• chr8-43140510-G-A
• rs1802477714
• NM_152419.3:c.14G>A

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.14G>A​(p.Gly5Asp) variant causes a missense 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 Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G5V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HGSNAT NM_152419.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.607
• 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=0.10629377).

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.14G>A	p.Gly5Asp	missense	Exon 1 of 18	NP_689632.2
	HGSNAT	NM_001363227.2		c.14G>A	p.Gly5Asp	missense	Exon 1 of 19	NP_001350156.1
	HGSNAT	NM_001363228.2		c.14G>A	p.Gly5Asp	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.14G>A	p.Gly5Asp	missense	Exon 1 of 18	ENSP00000368965.4	Q68CP4-2
	HGSNAT	ENST00000520704.1	TSL:1	n.-137G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000429109.1	E5RJC4
	HGSNAT	ENST00000520704.1	TSL:1	n.-137G>A		5_prime_UTR	Exon 1 of 10	ENSP00000429109.1	E5RJC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000219 AC: 2 AN: 914922 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 429192

African (AFR) AF: 0.00 AC: 0 AN: 17726

American (AMR) AF: 0.00 AC: 0 AN: 3266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7686

East Asian (EAS) AF: 0.000103 AC: 1 AN: 9728

South Asian (SAS) AF: 0.00 AC: 0 AN: 18038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2064

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 816028

Other (OTH) AF: 0.00 AC: 0 AN: 32218

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	-0.25	T
PhyloP100		0.61
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MVP		0.61
MPC		0.13
ClinPred		0.27	T
GERP RS		1.8
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.41
Mutation Taster		=89/11	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: rs1802477714; hg19: chr8-42995653;