4-11399380-A-C

Variant names:

• chr4-11399380-A-C
• rs774329981
• NM_005114.4:c.626T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

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]

ENSG00000308608 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST1	NM_005114.4	MANE Select	c.626T>G	p.Leu209Arg	missense	Exon 2 of 2	NP_005105.1	O14792

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST1	ENST00000002596.6	TSL:1 MANE Select	c.626T>G	p.Leu209Arg	missense	Exon 2 of 2	ENSP00000002596.5	O14792
	HS3ST1	ENST00000952062.1		c.626T>G	p.Leu209Arg	missense	Exon 3 of 3	ENSP00000622121.1
	HS3ST1	ENST00000952063.1		c.626T>G	p.Leu209Arg	missense	Exon 3 of 3	ENSP00000622122.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.1
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
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs774329981; hg19: chr4-11401004;