17-13496611-C-T

Variant names:

• chr17-13496611-C-T
• rs145257451
• NM_006042.3:c.807G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006042.3(HS3ST3A1):​c.807G>A​(p.Leu269Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000926 in 1,610,768 control chromosomes in the GnomAD database, including 11 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 0.0050 (8 hom., cov: 29)
  • Exomes 𝑓: 0.00050 (3 hom.)
• Consequence: HS3ST3A1 NM_006042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00505 (762/150986) while in subpopulation AFR AF = 0.0179 (730/40868). AF 95% confidence interval is 0.0168. There are 8 homozygotes in GnomAd4. There are 354 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.807G>A	p.Leu269Leu	synonymous	Exon 2 of 2	NP_006033.1	Q9Y663

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.807G>A	p.Leu269Leu	synonymous	Exon 2 of 2	ENSP00000284110.1	Q9Y663
	HS3ST3A1	ENST00000578576.1	TSL:3	c.201G>A	p.Leu67Leu	synonymous	Exon 2 of 2	ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 761 AN: 150868 Hom.: 8 Cov.: 29

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.00437

GnomAD2 exomes AF: 0.00113 AC: 260 AN: 230906 AF XY: 0.000885

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.000976

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000486

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000499 AC: 729 AN: 1459782 Hom.: 3 Cov.: 32 AF XY: 0.000414 AC XY: 301 AN XY: 726216

African (AFR) AF: 0.0182 AC: 607 AN: 33268

American (AMR) AF: 0.00115 AC: 51 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1110878

Other (OTH) AF: 0.00101 AC: 61 AN: 60270

GnomAD4 genome AF: 0.00505 AC: 762 AN: 150986 Hom.: 8 Cov.: 29 AF XY: 0.00480 AC XY: 354 AN XY: 73766

African (AFR) AF: 0.0179 AC: 730 AN: 40868

American (AMR) AF: 0.00105 AC: 16 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000885 AC: 6 AN: 67806

Other (OTH) AF: 0.00432 AC: 9 AN: 2082

Alfa AF: 0.000710 Hom.: 0

Bravo AF: 0.00610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		4.1
Mutation Taster		=98/2	polymorphism

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: rs145257451; hg19: chr17-13399928;