17-14301093-T-C

Variant names:

• chr17-14301093-T-C
• rs2072242
• NM_006041.3:c.-426T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006041.3(HS3ST3B1):​c.-426T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 185,222 control chromosomes in the GnomAD database, including 5,346 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 0.23 (4320 hom., cov: 34)
  • Exomes 𝑓: 0.23 (1026 hom.)
• Consequence: HS3ST3B1 NM_006041.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 6 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]

ENSG00000294706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

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.-426T>C		5_prime_UTR	Exon 1 of 2	NP_006032.1
	HS3ST3B1	NR_130138.2		n.13T>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.-426T>C		5_prime_UTR	Exon 1 of 2	ENSP00000354213.2
	HS3ST3B1	ENST00000466596.5	TSL:2	n.-426T>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436078.1
	ENSG00000294706	ENST00000725301.1		n.13A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35558 AN: 152146 Hom.: 4323 Cov.: 34

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.234 AC: 7712 AN: 32958 Hom.: 1026 Cov.: 0 AF XY: 0.240 AC XY: 3983 AN XY: 16576

African (AFR) AF: 0.237 AC: 263 AN: 1110

American (AMR) AF: 0.235 AC: 180 AN: 766

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 358 AN: 1250

East Asian (EAS) AF: 0.306 AC: 576 AN: 1880

South Asian (SAS) AF: 0.327 AC: 390 AN: 1194

European-Finnish (FIN) AF: 0.145 AC: 208 AN: 1430

Middle Eastern (MID) AF: 0.320 AC: 55 AN: 172

European-Non Finnish (NFE) AF: 0.226 AC: 5163 AN: 22860

Other (OTH) AF: 0.226 AC: 519 AN: 2296

GnomAD4 genome AF: 0.234 AC: 35577 AN: 152264 Hom.: 4320 Cov.: 34 AF XY: 0.232 AC XY: 17303 AN XY: 74458

African (AFR) AF: 0.205 AC: 8533 AN: 41572

American (AMR) AF: 0.228 AC: 3491 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5156

South Asian (SAS) AF: 0.415 AC: 2000 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1528 AN: 10610

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16420 AN: 68014

Other (OTH) AF: 0.266 AC: 563 AN: 2114

Alfa AF: 0.237 Hom.: 12118

Bravo AF: 0.238

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.92
PhyloP100		0.58
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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: rs2072242; hg19: chr17-14204410; COSMIC: COSV62906243; COSMIC: COSV62906243;