chr17-13543607-G-A

Variant names:

• chr17-13543607-G-A
• rs9913045
• NM_006042.3:c.600-46789C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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]

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

Our verdict: Benign. The variant received -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.

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.600-46789C>T		intron	N/A	NP_006033.1
	MIR548H3	NR_031679.1		n.40C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.600-46789C>T		intron	N/A	ENSP00000284110.1
	MIR548H3	ENST00000408771.1	TSL:6	n.40C>T		non_coding_transcript_exon	Exon 1 of 1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.-8+12336C>T		intron	N/A	ENSP00000462696.1

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

GnomAD2 exomes AF: 0.368 AC: 6554 AN: 17812 AF XY: 0.367

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 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

African (AFR) AF: 0.435 AC: 27 AN: 62

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.343 AC: 24 AN: 70

European-Finnish (FIN) AF: 0.326 AC: 3953 AN: 12144

Middle Eastern (MID) AF: 0.368 AC: 546 AN: 1484

European-Non Finnish (NFE) AF: 0.250 AC: 20 AN: 80

Other (OTH) AF: 0.470 AC: 110 AN: 234

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

African (AFR) AF: 0.663 AC: 27443 AN: 41402

American (AMR) AF: 0.401 AC: 6111 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1274 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1216 AN: 5036

South Asian (SAS) AF: 0.344 AC: 1645 AN: 4780

European-Finnish (FIN) AF: 0.350 AC: 3660 AN: 10472

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24355 AN: 67784

Other (OTH) AF: 0.429 AC: 900 AN: 2098

Alfa AF: 0.409 Hom.: 1814

Bravo AF: 0.456

Asia WGS AF: 0.343 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.30
PhyloP100		0.36
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: rs9913045; hg19: chr17-13446924; COSMIC: COSV52374074;