rs9488363

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST5	NM_153612.4	c.-338-42044T>C		intron_variant		ENST00000312719.10
HDAC2-AS2	NR_125845.1	n.1799+35051A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST5	ENST00000312719.10	c.-338-42044T>C		intron_variant		2	NM_153612.4	P1
HDAC2-AS2	ENST00000519104.5	n.1799+35051A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.542

Alfa AF: 0.519 Hom.: 13181

Bravo AF: 0.545

Asia WGS AF: 0.581 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.59

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: rs9488363; hg19: chr6-114591986;