Variant 4-11399987-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005114.4(HS3ST1):c.19G>C(p.Gly7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000029 in 1,379,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HS3ST1
NM_005114.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

HS3ST1 (HGNC:5194): (heparan sulfate-glucosamine 3-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It possesses both heparan sulfate glucosaminyl 3-O-sulfotransferase activity, anticoagulant heparan sulfate conversion activity, and is a rate limiting enzyme for synthesis of anticoagulant heparan. This enzyme is an intraluminal Golgi resident protein. [provided by RefSeq, Jul 2008]

HS3ST1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST1	NM_005114.4 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/2	ENST00000002596.6	NP_005105.1
HS3ST1	XM_011513913.4 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/2		XP_011512215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HS3ST1	ENST00000002596.6 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/2	1	NM_005114.4	ENSP00000002596	P1
HS3ST1	ENST00000510712.1 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/2	2		ENSP00000422629
HS3ST1	ENST00000514690.5 linkuse as main transcript	c.19G>C	p.Gly7Arg	missense_variant	2/2	3		ENSP00000425673

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1379724

Hom.:

Cov.:

AF XY:

0.00000441

AC XY:

AN XY:

680086

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:

9.30e-7

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.19G>C (p.G7R) alteration is located in exon 2 (coding exon 1) of the HS3ST1 gene. This alteration results from a G to C substitution at nucleotide position 19, causing the glycine (G) at amino acid position 7 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

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;.;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0050

D;.;.

Polyphen

1.0

D;.;.

Vest4

0.67

MutPred

0.57

Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);

MVP

0.70

MPC

0.53

ClinPred

0.92

GERP RS

5.5

Varity_R

0.27

gMVP

0.70

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