17-14301765-G-C

Position:

• chr17-14301765-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000360954.3(HS3ST3B1):​c.247G>C​(p.Gly83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,577,038 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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: 𝑓 0.0071 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (15 hom.)
• Consequence: HS3ST3B1 ENST00000360954.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033798218).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00705 (1074/152280) while in subpopulation AFR AF= 0.0238 (991/41562). AF 95% confidence interval is 0.0226. There are 11 homozygotes in gnomad4. There are 523 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3	c.247G>C	p.Gly83Arg	missense_variant	1/2	ENST00000360954.3	NP_006032.1
HS3ST3B1	NR_130138.2	n.685G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3	c.247G>C	p.Gly83Arg	missense_variant	1/2	1	NM_006041.3	ENSP00000354213	P1
HS3ST3B1	ENST00000466596.5	c.247G>C	p.Gly83Arg	missense_variant, NMD_transcript_variant	1/3	2		ENSP00000436078

Frequencies

GnomAD3 genomes AF: 0.00707 AC: 1076 AN: 152166 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00178 AC: 325 AN: 182906 Hom.: 3 AF XY: 0.00131 AC XY: 131 AN XY: 100316

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000756

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000277

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.000952 AC: 1356 AN: 1424758 Hom.: 15 Cov.: 31 AF XY: 0.000839 AC XY: 592 AN XY: 705394

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.0000964

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000249

Gnomad4 OTH exome AF: 0.00213

GnomAD4 genome AF: 0.00705 AC: 1074 AN: 152280 Hom.: 11 Cov.: 33 AF XY: 0.00702 AC XY: 523 AN XY: 74474

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.000785 Hom.: 0

Bravo AF: 0.00800

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00491 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00160 AC: 173

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.5
DANN	Benign	0.77
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.045
Sift	Benign	0.21	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.042
MutPred		0.22		Gain of methylation at G83 (P = 0.0432);
MVP		0.10
ClinPred		0.0049	T
GERP RS		-1.6
Varity_R		0.036
gMVP		0.59

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

Other links and lift over

dbSNP: rs62636623; hg19: chr17-14205082;