rs9913045

Positions:

• chr17-13543607-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006042.3(HS3ST3A1):​c.600-46789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 165,562 control chromosomes in the GnomAD database, including 17,173 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 0.44 (16372 hom., cov: 30)
  • Exomes 𝑓: 0.33 (801 hom.)
• Consequence: HS3ST3A1 NM_006042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

MIR548H3 (HGNC:35344): (microRNA 548h-3) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.600-46789C>T		intron_variant		ENST00000284110.2	NP_006033.1
MIR548H3	NR_031679.1	n.40C>T		non_coding_transcript_exon_variant	1/1
HS3ST3A1	XM_011524114.4	c.-3195C>T		5_prime_UTR_variant	1/3		XP_011522416.1
HS3ST3A1	XM_047437228.1	c.-4539C>T		5_prime_UTR_variant	1/2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.600-46789C>T		intron_variant		1	NM_006042.3	ENSP00000284110	P1
MIR548H3	ENST00000408771.1	n.40C>T		mature_miRNA_variant	1/1
HS3ST3A1	ENST00000578576.1	c.-8+12336C>T		intron_variant		3		ENSP00000462696

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66890 AN: 151366 Hom.: 16345 Cov.: 30

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.427

GnomAD3 exomes AF: 0.368 AC: 6554 AN: 17812 Hom.: 1275 AF XY: 0.367 AC XY: 2854 AN XY: 7786

Gnomad AFR exome AF: 0.679

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.333 AC: 4681 AN: 14078 Hom.: 801 Cov.: 0 AF XY: 0.332 AC XY: 2260 AN XY: 6800

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.442 AC: 66986 AN: 151484 Hom.: 16372 Cov.: 30 AF XY: 0.437 AC XY: 32322 AN XY: 74010

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.429

Alfa AF: 0.399 Hom.: 1646

Bravo AF: 0.456

Asia WGS AF: 0.343 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.30

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: rs9913045; hg19: chr17-13446924; COSMIC: COSV52374074;