Variant 8-43140516-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_152419.3(HGSNAT):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 931,868 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

HGSNAT
NM_152419.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.978

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:

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ACMG classification

Classification made for transcript

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=0.16137758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGSNAT	NM_152419.3 link	c.20C>T	p.Ala7Val	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 link	c.20C>T	p.Ala7Val	missense_variant	1/18	2	NM_152419.3	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000520704.1 link	n.-131C>T		non_coding_transcript_exon_variant	1/10	1		ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000520704.1 link	n.-131C>T		5_prime_UTR_variant	1/10	1		ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000517319.1 link	n.20C>T		non_coding_transcript_exon_variant	1/5	4		ENSP00000430032.1	E5RH11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000322

AC:

AN:

931868

Hom.:

Cov.:

AF XY:

0.00000456

AC XY:

AN XY:

438126

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:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.40

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.42

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.066

MVP

0.53

MPC

0.10

ClinPred

0.49

GERP RS

-0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over