rs9488363

Variant names:

• chr6-114270822-A-G
• rs9488363
• NM_153612.4:c.-338-42044T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-114270822-A-G
• chr6-114270822-A-T

Variant summary

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

The NM_153612.4(HS3ST5):​c.-338-42044T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,886 control chromosomes in the GnomAD database, including 22,829 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 0.55 (22829 hom., cov: 32)
• Consequence: HS3ST5 NM_153612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 9 publications found

Genes affected

HS3ST5 (HGNC:19419): (heparan sulfate-glucosamine 3-sulfotransferase 5) HS3ST5 belongs to a group of heparan sulfate 3-O-sulfotransferases (EC 2.8.2.23) that transfer sulfate from 3-prime-phosphoadenosine 5-prime phosphosulfate (PAPS) to heparan sulfate and heparin (Mochizuki et al., 2003 [PubMed 12740361]).[supplied by OMIM, Mar 2008]

HDAC2-AS2 (HGNC:43590): (HDAC2 and HS3ST5 antisense RNA 2)

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 = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153612.4. 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
	HS3ST5	NM_153612.4	MANE Select	c.-338-42044T>C		intron	N/A	NP_705840.2
	HS3ST5	NM_001387039.1		c.-226-42044T>C		intron	N/A	NP_001373968.1	Q8IZT8
	HS3ST5	NM_001387040.1		c.-33+71373T>C		intron	N/A	NP_001373969.1	Q8IZT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST5	ENST00000312719.10	TSL:2 MANE Select	c.-338-42044T>C		intron	N/A	ENSP00000427888.1	Q8IZT8
	HDAC2-AS2	ENST00000519104.5	TSL:1	n.1799+35051A>G		intron	N/A
	HS3ST5	ENST00000900060.1		c.-431-42044T>C		intron	N/A	ENSP00000570119.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82830 AN: 151768 Hom.: 22789 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.546 AC: 82932 AN: 151886 Hom.: 22829 Cov.: 32 AF XY: 0.548 AC XY: 40659 AN XY: 74220

African (AFR) AF: 0.625 AC: 25878 AN: 41418

American (AMR) AF: 0.510 AC: 7772 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2632 AN: 5148

South Asian (SAS) AF: 0.528 AC: 2544 AN: 4814

European-Finnish (FIN) AF: 0.549 AC: 5792 AN: 10546

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34432 AN: 67936

Other (OTH) AF: 0.542 AC: 1146 AN: 2114

Alfa AF: 0.534 Hom.: 20471

Bravo AF: 0.545

Asia WGS AF: 0.581 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-1.1
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: rs9488363; hg19: chr6-114591986; COSMIC: COSV107358550;