NM_005114.4:c.870T>G

Variant names:

• chr4-11399136-A-C
• rs1360121288
• NM_005114.4:c.870T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005114.4(HS3ST1):​c.870T>G​(p.His290Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HS3ST1 NM_005114.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097643524).

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.870T>G	p.His290Gln	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.870T>G	p.His290Gln	missense	Exon 2 of 2	ENSP00000002596.5	O14792
	HS3ST1	ENST00000952062.1		c.870T>G	p.His290Gln	missense	Exon 3 of 3	ENSP00000622121.1
	HS3ST1	ENST00000952063.1		c.870T>G	p.His290Gln	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	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	1.3
DANN	Benign	0.85
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	N
PhyloP100		-0.45
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.24
Sift	Benign	0.22	T
Sift4G	Benign	0.42	T
Polyphen		0.015	B
Vest4		0.22
MutPred		0.43		Gain of ubiquitination at K294 (P = 0.0837)
MVP		0.37
MPC		0.46
ClinPred		0.17	T
GERP RS		-3.9
Varity_R		0.32
gMVP		0.40
Mutation Taster		=65/35	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: rs1360121288; hg19: chr4-11400760;