chr17-14345850-C-T

Position:

• chr17-14345850-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006041.3(HS3ST3B1):​c.*204C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 619,588 control chromosomes in the GnomAD database, including 116,332 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (22164 hom., cov: 32)
  • Exomes 𝑓: 0.63 (94168 hom.)
• Consequence: HS3ST3B1 NM_006041.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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]

HS3ST3B1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3	c.*204C>T		3_prime_UTR_variant	2/2	ENST00000360954.3	NP_006032.1
HS3ST3B1	XM_017025479.3	c.*204C>T		3_prime_UTR_variant	2/2		XP_016880968.1
HS3ST3B1	NR_130138.2	n.1667+148C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3	c.*204C>T		3_prime_UTR_variant	2/2	1	NM_006041.3	ENSP00000354213.2
HS3ST3B1	ENST00000466596.5	n.*56+148C>T		intron_variant		2		ENSP00000436078.1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74993 AN: 152030 Hom.: 22164 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.628 AC: 293368 AN: 467438 Hom.: 94168 Cov.: 7 AF XY: 0.629 AC XY: 149145 AN XY: 236970

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.657

Gnomad4 OTH exome AF: 0.587

GnomAD4 genome AF: 0.493 AC: 74993 AN: 152150 Hom.: 22164 Cov.: 32 AF XY: 0.496 AC XY: 36856 AN XY: 74372

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.495

Alfa AF: 0.608 Hom.: 39923

Bravo AF: 0.461

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.61

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: rs3785655; hg19: chr17-14249167; COSMIC: COSV62907252;