rs774329981

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005114.4(HS3ST1):​c.626T>G​(p.Leu209Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. L209P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

HS3ST1
NM_005114.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.14
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26658335).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HS3ST1NM_005114.4 linkc.626T>G p.Leu209Arg missense_variant Exon 2 of 2 ENST00000002596.6 NP_005105.1 O14792A0A024R9R4
HS3ST1XM_011513913.4 linkc.626T>G p.Leu209Arg missense_variant Exon 2 of 2 XP_011512215.1 O14792A0A024R9R4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HS3ST1ENST00000002596.6 linkc.626T>G p.Leu209Arg missense_variant Exon 2 of 2 1 NM_005114.4 ENSP00000002596.5 O14792

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
14
DANN
Uncertain
0.97
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.059
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
0.61
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
1.1
N
REVEL
Uncertain
0.43
Sift
Benign
0.41
T
Sift4G
Benign
0.55
T
Polyphen
0.67
P
Vest4
0.32
MutPred
0.49
Gain of solvent accessibility (P = 0.0018);
MVP
0.76
MPC
0.73
ClinPred
0.39
T
GERP RS
5.6
Varity_R
0.50
gMVP
0.67

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: rs774329981; hg19: chr4-11401004; API