Genetic Variant NM_152419.3:c.28G>A (chr8-43140524-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152419.3(HGSNAT):c.28G>A(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 952,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HGSNAT
NM_152419.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

0 publications found

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 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: Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 73
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HGSNAT links:

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ACMG classification

Classification was made for transcript

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=0.10419813).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HGSNAT	NM_152419.3	MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 18	NP_689632.2
HGSNAT	NM_001363227.2		c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	NP_001350156.1
HGSNAT	NM_001363228.2		c.28G>A	p.Ala10Thr	missense	Exon 1 of 16	NP_001350157.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HGSNAT	ENST00000379644.9	TSL:2 MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 18	ENSP00000368965.4	Q68CP4-2
HGSNAT	ENST00000520704.1	TSL:1	n.-123G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000429109.1	E5RJC4
HGSNAT	ENST00000520704.1	TSL:1	n.-123G>A		5_prime_UTR	Exon 1 of 10	ENSP00000429109.1	E5RJC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000210

AC:

AN:

952324

Hom.:

Cov.:

AF XY:

0.00000223

AC XY:

AN XY:

448804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18616

American (AMR)

AF:

0.00

AC:

AN:

4282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8954

East Asian (EAS)

AF:

0.00

AC:

AN:

13552

South Asian (SAS)

AF:

0.00

AC:

AN:

18736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2240

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

839916

Other (OTH)

AF:

0.00

AC:

AN:

34546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.63

PhyloP100

-0.25

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.23

REVEL

Benign

0.20

Sift

Benign

0.20

Sift4G

Benign

0.41

Vest4

0.082

MVP

0.56

MPC

0.098

ClinPred

0.13

GERP RS

0.93

PromoterAI

-0.083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.40

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over