17-13601372-T-A

Position:

• chr17-13601372-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006042.3(HS3ST3A1):​c.-243A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 471,604 control chromosomes in the GnomAD database, including 303 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 0.012 (74 hom., cov: 33)
  • Exomes 𝑓: 0.020 (229 hom.)
• Consequence: HS3ST3A1 NM_006042.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.-243A>T		5_prime_UTR_variant	1/2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_017025480.3	c.-243A>T		5_prime_UTR_variant	1/2		XP_016880969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.-243A>T		5_prime_UTR_variant	1/2	1	NM_006042.3	ENSP00000284110.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1870 AN: 152150 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0203 AC: 6489 AN: 319336 Hom.: 229 Cov.: 0 AF XY: 0.0213 AC XY: 3533 AN XY: 166084

Gnomad4 AFR exome AF: 0.00302

Gnomad4 AMR exome AF: 0.00357

Gnomad4 ASJ exome AF: 0.00431

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0549

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.00778

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.0123 AC: 1872 AN: 152268 Hom.: 74 Cov.: 33 AF XY: 0.0138 AC XY: 1031 AN XY: 74456

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0642

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.00722

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00868 Hom.: 4

Bravo AF: 0.00909

Asia WGS AF: 0.0980 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.89

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: rs3744336; hg19: chr17-13504689;