chr17-14345106-T-C

Variant names:

• chr17-14345106-T-C
• rs9906855
• NM_006041.3:c.633T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006041.3(HS3ST3B1):​c.633T>C​(p.Pro211Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 149,386 control chromosomes in the GnomAD database, including 27,369 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 0.57 (27369 hom., cov: 25)
  • Exomes 𝑓: 0.70 (338642 hom.)
  • Failed GnomAD Quality Control
• Consequence: HS3ST3B1 NM_006041.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 10 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3	c.633T>C	p.Pro211Pro	synonymous_variant	Exon 2 of 2	ENST00000360954.3	NP_006032.1
HS3ST3B1	XM_017025479.3	c.72T>C	p.Pro24Pro	synonymous_variant	Exon 2 of 2		XP_016880968.1
HS3ST3B1	NR_130138.2	n.1071T>C		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3	c.633T>C	p.Pro211Pro	synonymous_variant	Exon 2 of 2	1	NM_006041.3	ENSP00000354213.2
HS3ST3B1	ENST00000466596.5	n.633T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000436078.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 84856 AN: 149274 Hom.: 27368 Cov.: 25

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.561

GnomAD2 exomes AF: 0.503 AC: 91744 AN: 182240 AF XY: 0.508

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.546

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.482

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.701 AC: 858872 AN: 1225270 Hom.: 338642 Cov.: 47 AF XY: 0.694 AC XY: 421318 AN XY: 606808

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.185 AC: 5521 AN: 29816

American (AMR) AF: 0.348 AC: 12509 AN: 35946

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 11146 AN: 21720

East Asian (EAS) AF: 0.591 AC: 21802 AN: 36902

South Asian (SAS) AF: 0.598 AC: 42688 AN: 71396

European-Finnish (FIN) AF: 0.734 AC: 36063 AN: 49158

Middle Eastern (MID) AF: 0.524 AC: 2682 AN: 5120

European-Non Finnish (NFE) AF: 0.750 AC: 692916 AN: 923584

Other (OTH) AF: 0.650 AC: 33545 AN: 51628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.568 AC: 84862 AN: 149386 Hom.: 27369 Cov.: 25 AF XY: 0.568 AC XY: 41318 AN XY: 72750

African (AFR) AF: 0.252 AC: 10330 AN: 40974

American (AMR) AF: 0.561 AC: 8396 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2060 AN: 3438

East Asian (EAS) AF: 0.595 AC: 2975 AN: 4996

South Asian (SAS) AF: 0.644 AC: 2959 AN: 4598

European-Finnish (FIN) AF: 0.741 AC: 7524 AN: 10156

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 48738 AN: 67014

Other (OTH) AF: 0.562 AC: 1165 AN: 2072

Alfa AF: 0.504 Hom.: 3270

Bravo AF: 0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		-2.0
Mutation Taster		=96/4	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: rs9906855; hg19: chr17-14248423; COSMIC: COSV62906476;