17-13601157-C-T

Variant names:

• chr17-13601157-C-T
• rs73298111
• NM_006042.3:c.-28G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006042.3(HS3ST3A1):​c.-28G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,478,940 control chromosomes in the GnomAD database, including 9,361 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 0.12 (1134 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8227 hom.)
• Consequence: HS3ST3A1 NM_006042.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 7 publications found

Genes affected

HS3ST3A1 (HGNC:5196): (heparan sulfate-glucosamine 3-sulfotransferase 3A1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. The sulfotransferase domain of this enzyme is highly similar to the same domain of heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3B1, and these two enzymes sulfate an identical disaccharide. This gene is widely expressed, with the most abundant expression in liver and placenta. [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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 2	NP_006033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 2	ENSP00000284110.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17901 AN: 152140 Hom.: 1134 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.0965 AC: 8618 AN: 89328 AF XY: 0.0972

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0582

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0143

Gnomad FIN exome AF: 0.0756

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.108 AC: 143477 AN: 1326686 Hom.: 8227 Cov.: 26 AF XY: 0.108 AC XY: 70096 AN XY: 651308

African (AFR) AF: 0.170 AC: 4724 AN: 27714

American (AMR) AF: 0.0636 AC: 1752 AN: 27556

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2451 AN: 20838

East Asian (EAS) AF: 0.0379 AC: 1218 AN: 32116

South Asian (SAS) AF: 0.0898 AC: 6096 AN: 67908

European-Finnish (FIN) AF: 0.0757 AC: 3352 AN: 44282

Middle Eastern (MID) AF: 0.140 AC: 642 AN: 4574

European-Non Finnish (NFE) AF: 0.112 AC: 117237 AN: 1046772

Other (OTH) AF: 0.109 AC: 6005 AN: 54926

GnomAD4 genome AF: 0.118 AC: 17916 AN: 152254 Hom.: 1134 Cov.: 33 AF XY: 0.113 AC XY: 8386 AN XY: 74448

African (AFR) AF: 0.162 AC: 6728 AN: 41560

American (AMR) AF: 0.0848 AC: 1297 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3472

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5170

South Asian (SAS) AF: 0.0902 AC: 436 AN: 4832

European-Finnish (FIN) AF: 0.0727 AC: 772 AN: 10626

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7705 AN: 67982

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.0739 Hom.: 149

Bravo AF: 0.121

Asia WGS AF: 0.0580 AC: 204 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		-0.53
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: rs73298111; hg19: chr17-13504474; COSMIC: COSV52379150;