rs10492589

Variant names:

• chr13-96208669-A-T
• rs10492589
• NM_153456.4:c.707+117100A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153456.4(HS6ST3):​c.707+117100A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 152,304 control chromosomes in the GnomAD database, including 205 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 0.041 (205 hom., cov: 33)
• Consequence: HS6ST3 NM_153456.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 2 publications found

Genes affected

HS6ST3 (HGNC:19134): (heparan sulfate 6-O-sulfotransferase 3) Heparan sulfate (HS) sulfotransferases, such as HS6ST3, modify HS to generate structures required for interactions between HS and a variety of proteins. These interactions are implicated in proliferation and differentiation, adhesion, migration, inflammation, blood coagulation, and other diverse processes (Habuchi et al., 2000 [PubMed 10644753]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4	c.707+117100A>T		intron_variant	Intron 1 of 1	ENST00000376705.4	NP_703157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4	c.707+117100A>T		intron_variant	Intron 1 of 1	1	NM_153456.4	ENSP00000365895.2

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6219 AN: 152186 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0409 AC: 6231 AN: 152304 Hom.: 205 Cov.: 33 AF XY: 0.0405 AC XY: 3018 AN XY: 74482

African (AFR) AF: 0.0868 AC: 3607 AN: 41566

American (AMR) AF: 0.0154 AC: 236 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.0553 AC: 287 AN: 5188

South Asian (SAS) AF: 0.0448 AC: 216 AN: 4822

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1512 AN: 68032

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0344 Hom.: 16

Bravo AF: 0.0406

Asia WGS AF: 0.0360 AC: 125 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.52
PhyloP100		-0.79
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: rs10492589; hg19: chr13-96860923;