chr17-14301571-T-C

Variant names:

• chr17-14301571-T-C
• rs200257944
• NM_006041.3:c.53T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006041.3(HS3ST3B1):​c.53T>C​(p.Leu18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,443,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L18H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: HS3ST3B1 NM_006041.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15205011).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	NM_006041.3	MANE Select	c.53T>C	p.Leu18Pro	missense	Exon 1 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.491T>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.53T>C	p.Leu18Pro	missense	Exon 1 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.53T>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1	Q9Y662

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000554 AC: 8 AN: 1443848 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 718556

African (AFR) AF: 0.000244 AC: 8 AN: 32782

American (AMR) AF: 0.00 AC: 0 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.00 AC: 0 AN: 85468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109306

Other (OTH) AF: 0.00 AC: 0 AN: 59910

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.052
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.095	T
Polyphen		0.0	B
Vest4		0.51
MutPred		0.19		Gain of glycosylation at L18 (P = 0.0181)
MVP		0.21
ClinPred		0.13	T
GERP RS		3.0
PromoterAI		0.017	Neutral
Varity_R		0.11
gMVP		0.72
Mutation Taster		=84/16	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: rs200257944; hg19: chr17-14204888;