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GeneBe

8-43140508-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_152419.3(HGSNAT):c.12G>A(p.Ala4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,058,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

HGSNAT
NM_152419.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.412
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-43140508-G-A is Benign according to our data. Variant chr8-43140508-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 761828.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.412 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HGSNATNM_152419.3 linkuse as main transcriptc.12G>A p.Ala4= synonymous_variant 1/18 ENST00000379644.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HGSNATENST00000379644.9 linkuse as main transcriptc.12G>A p.Ala4= synonymous_variant 1/182 NM_152419.3 P3Q68CP4-2
HGSNATENST00000520704.1 linkuse as main transcriptc.-139G>A 5_prime_UTR_variant, NMD_transcript_variant 1/101
HGSNATENST00000517319.1 linkuse as main transcriptc.12G>A p.Ala4= synonymous_variant, NMD_transcript_variant 1/54

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000770
AC:
114
AN:
148084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00268
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000201
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:
0.00
Gnomad OTH
AF:
0.000490
GnomAD4 exome
AF:
0.0000450
AC:
41
AN:
910198
Hom.:
1
Cov.:
29
AF XY:
0.0000398
AC XY:
17
AN XY:
426748
show subpopulations
Gnomad4 AFR exome
AF:
0.00193
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:
0.00
Gnomad4 OTH exome
AF:
0.000219
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000769
AC:
114
AN:
148192
Hom.:
0
Cov.:
32
AF XY:
0.000651
AC XY:
47
AN XY:
72230
show subpopulations
Gnomad4 AFR
AF:
0.00267
Gnomad4 AMR
AF:
0.000201
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000484
Alfa
AF:
0.0000713
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-III-C Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Nov 11, 2019- -
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
6.4
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs1018475767; hg19: chr8-42995651; API