rs797045120

chr8-43158949-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_152419.3(HGSNAT):c.398G>C(p.Gly133Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HGSNAT NM_152419.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.22

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927
• PP5: Variant 8-43158949-G-C is Pathogenic according to our data. Variant chr8-43158949-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 208814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-43158949-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGSNAT	NM_152419.3	c.398G>C	p.Gly133Ala	missense_variant	4/18	ENST00000379644.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGSNAT	ENST00000379644.9	c.398G>C	p.Gly133Ala	missense_variant	4/18	2	NM_152419.3	P3
HGSNAT	ENST00000520704.1	c.248G>C	p.Gly83Ala	missense_variant, NMD_transcript_variant	4/10	1
HGSNAT	ENST00000517319.1	c.261G>C	p.Trp87Cys	missense_variant, NMD_transcript_variant	3/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 73 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
Cadd	Pathogenic	26
Dann	Benign	0.92
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Pathogenic	0.97	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.91
MVP		0.92
MPC		0.53
ClinPred		0.90	D
GERP RS		6.0
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs797045120; hg19: chr8-43014092;