chr8-43140510-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HGSNAT NM_152419.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a topological_domain Lumenal, vesicle (size 189) in uniprot entity HGNAT_HUMAN there are 13 pathogenic changes around while only 1 benign (93%) in NM_152419.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10629377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGSNAT	NM_152419.3	c.14G>A	p.Gly5Asp	missense_variant	Exon 1 of 18	ENST00000379644.9	NP_689632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGSNAT	ENST00000379644.9	c.14G>A	p.Gly5Asp	missense_variant	Exon 1 of 18	2	NM_152419.3	ENSP00000368965.4
HGSNAT	ENST00000520704.1	n.-137G>A		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000429109.1
HGSNAT	ENST00000520704.1	n.-137G>A		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000429109.1
HGSNAT	ENST00000517319.1	n.14G>A		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000430032.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000123

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1802477714; hg19: chr8-42995653;