chrX-132669122-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001394073.1(HS6ST2):ā€‹c.1058A>Gā€‹(p.Lys353Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,199,174 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes š‘“: 0.000084 ( 0 hom. 54 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07
Variant links:
Genes affected
HS6ST2 (HGNC:19133): (heparan sulfate 6-O-sulfotransferase 2) Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
HS6ST2-AS1 (HGNC:40870): (HS6ST2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03985825).
BS2
High Hemizygotes in GnomAdExome4 at 54 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HS6ST2NM_001394073.1 linkuse as main transcriptc.1058A>G p.Lys353Arg missense_variant 4/5 ENST00000370833.7 NP_001381002.1
HS6ST2-AS1NR_046691.1 linkuse as main transcriptn.225-441T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HS6ST2ENST00000370833.7 linkuse as main transcriptc.1058A>G p.Lys353Arg missense_variant 4/55 NM_001394073.1 ENSP00000359870 Q96MM7-4
HS6ST2-AS1ENST00000455269.1 linkuse as main transcriptn.225-441T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000179
AC:
2
AN:
111824
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33964
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000766
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000130
AC:
23
AN:
176793
Hom.:
0
AF XY:
0.000264
AC XY:
17
AN XY:
64293
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00126
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000837
AC:
91
AN:
1087299
Hom.:
0
Cov.:
26
AF XY:
0.000153
AC XY:
54
AN XY:
353611
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:
0.00155
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000175
GnomAD4 genome
AF:
0.0000179
AC:
2
AN:
111875
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34025
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000769
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.000174
AC:
21

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 28, 2023The c.1058A>G (p.K353R) alteration is located in exon 5 (coding exon 4) of the HS6ST2 gene. This alteration results from a A to G substitution at nucleotide position 1058, causing the lysine (K) at amino acid position 353 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
19
DANN
Uncertain
0.99
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.46
.;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.040
T;T;T
MetaSVM
Benign
-0.61
T
MutationTaster
Benign
1.0
D;D;D;N;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.25
N;.;.
REVEL
Benign
0.26
Sift
Benign
0.13
T;.;.
Sift4G
Benign
0.35
T;T;.
Vest4
0.22
MVP
0.63
MPC
0.57
ClinPred
0.58
D
GERP RS
4.1
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs767217888; hg19: chrX-131803150; API