17-14345560-G-C

Variant names:

• chr17-14345560-G-C
• rs9906590
• NM_006041.3:c.1087G>C

Variant summary

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

The NM_006041.3(HS3ST3B1):​c.1087G>C​(p.Glu363Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: HS3ST3B1 NM_006041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 4 publications found

Genes affected

HS3ST3B1 (HGNC:5198): (heparan sulfate-glucosamine 3-sulfotransferase 3B1) The protein encoded by this gene is a type II integral membrane protein that belongs to the 3-O-sulfotransferases family. These proteins catalyze the addition of sulfate groups at the 3-OH position of glucosamine in heparan sulfate. The substrate specificity of individual members of the family is based on prior modification of the heparan sulfate chain, thus allowing different members of the family to generate binding sites for different proteins on the same heparan sulfate chain. Following treatment with a histone deacetylase inhibitor, expression of this gene is activated in a pancreatic cell line. The increased expression results in promotion of the epithelial-mesenchymal transition. In addition, the modification catalyzed by this protein allows herpes simplex virus membrane fusion and penetration. A very closely related homolog with an almost identical sulfotransferase domain maps less than 1 Mb away. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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=0.16751099).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	NM_006041.3	MANE Select	c.1087G>C	p.Glu363Gln	missense	Exon 2 of 2	NP_006032.1
	HS3ST3B1	NR_130138.2		n.1525G>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.1087G>C	p.Glu363Gln	missense	Exon 2 of 2	ENSP00000354213.2
	HS3ST3B1	ENST00000466596.5	TSL:2	n.1087G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000436078.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433362 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 710896

African (AFR) AF: 0.00 AC: 0 AN: 32762

American (AMR) AF: 0.00 AC: 0 AN: 40440

Ashkenazi Jewish (ASJ) AF: 0.0000421 AC: 1 AN: 23742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 79898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099600

Other (OTH) AF: 0.00 AC: 0 AN: 59284

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 7

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.27
Sift	Benign	0.15	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.049
MutPred		0.53		Gain of MoRF binding (P = 0.0244)
MVP		0.82
ClinPred		0.67	D
GERP RS		3.9
Varity_R		0.18
gMVP		0.45

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: rs9906590; hg19: chr17-14248877;