NM_006041.3:c.*204C>T

Variant names:

• chr17-14345850-C-T
• rs3785655
• NM_006041.3:c.*204C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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: Benign. The variant received -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.

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.*204C>T		3_prime_UTR	Exon 2 of 2	NP_006032.1	Q9Y662
	HS3ST3B1	NR_130138.2		n.1667+148C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.*204C>T		3_prime_UTR	Exon 2 of 2	ENSP00000354213.2	Q9Y662
	HS3ST3B1	ENST00000466596.5	TSL:2	n.*56+148C>T		intron	N/A	ENSP00000436078.1	Q9Y662

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

African (AFR) AF: 0.146 AC: 1677 AN: 11448

American (AMR) AF: 0.467 AC: 5356 AN: 11462

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 6985 AN: 12044

East Asian (EAS) AF: 0.561 AC: 15193 AN: 27072

South Asian (SAS) AF: 0.629 AC: 13826 AN: 21966

European-Finnish (FIN) AF: 0.669 AC: 23354 AN: 34918

Middle Eastern (MID) AF: 0.532 AC: 970 AN: 1824

European-Non Finnish (NFE) AF: 0.657 AC: 211490 AN: 321984

Other (OTH) AF: 0.587 AC: 14517 AN: 24720

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

African (AFR) AF: 0.152 AC: 6317 AN: 41508

American (AMR) AF: 0.494 AC: 7560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2002 AN: 3466

East Asian (EAS) AF: 0.569 AC: 2951 AN: 5182

South Asian (SAS) AF: 0.634 AC: 3064 AN: 4832

European-Finnish (FIN) AF: 0.666 AC: 7045 AN: 10572

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44283 AN: 67986

Other (OTH) AF: 0.495 AC: 1044 AN: 2108

Alfa AF: 0.590 Hom.: 52674

Bravo AF: 0.461

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		0.13
Mutation Taster		=100/0	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: rs3785655; hg19: chr17-14249167; COSMIC: COSV62907252;