chr17-13543607-G-A

Position:

• 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:):

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

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	ENSP00000284110.1
HS3ST3A1	ENST00000578576.1	c.-8+12336C>T		intron_variant		3		ENSP00000462696.1
MIR548H3	ENST00000408771.1	n.40C>T		non_coding_transcript_exon_variant	1/1	6

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;