Variant 8-43140506-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_ModerateBP6_Moderate

The NM_152419.3(HGSNAT):c.10G>C(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000715 in 1,048,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

HGSNAT
NM_152419.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.862

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 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=0.16627198).

BP6

Variant 8-43140506-G-C is Benign according to our data. Variant chr8-43140506-G-C is described in ClinVar as [Benign]. Clinvar id is 2139887.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGSNAT	NM_152419.3 linkuse as main transcript	c.10G>C	p.Ala4Pro	missense_variant	1/18	ENST00000379644.9	NP_689632.2	Q68CP4-2Q8IVU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HGSNAT	ENST00000379644.9 linkuse as main transcript	c.10G>C	p.Ala4Pro	missense_variant	1/18	2	NM_152419.3	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000520704.1 linkuse as main transcript	n.-141G>C		non_coding_transcript_exon_variant	1/10	1		ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000520704.1 linkuse as main transcript	n.-141G>C		5_prime_UTR_variant	1/10	1		ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000517319.1 linkuse as main transcript	n.10G>C		non_coding_transcript_exon_variant	1/5	4		ENSP00000430032.1	E5RH11

Frequencies

GnomAD3 genomes

AF:

0.0000406

AC:

AN:

147748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000604

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

AN:

901050

Hom.:

Cov.:

AF XY:

0.0000711

AC XY:

AN XY:

421998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000856

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000406

AC:

AN:

147748

Hom.:

Cov.:

AF XY:

0.0000556

AC XY:

AN XY:

71966

show subpopulations

Gnomad4 AFR

AF:

0.0000488

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000604

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.58

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.21

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.16

MVP

0.61

MPC

0.13

ClinPred

0.26

GERP RS

-0.16

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over