6-114125959-C-T

Variant names:

• chr6-114125959-C-T
• rs1519686
• NM_153612.4:c.-33+42392G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153612.4(HS3ST5):​c.-33+42392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,002 control chromosomes in the GnomAD database, including 4,853 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 0.25 (4853 hom., cov: 32)
• Consequence: HS3ST5 NM_153612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST5	NM_153612.4	c.-33+42392G>A		intron_variant	Intron 3 of 4	ENST00000312719.10	NP_705840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST5	ENST00000312719.10	c.-33+42392G>A		intron_variant	Intron 3 of 4	2	NM_153612.4	ENSP00000427888.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37951 AN: 151884 Hom.: 4852 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.250 AC: 37971 AN: 152002 Hom.: 4853 Cov.: 32 AF XY: 0.248 AC XY: 18426 AN XY: 74248

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.238

Alfa AF: 0.212 Hom.: 1735

Bravo AF: 0.243

Asia WGS AF: 0.190 AC: 659 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	1.3
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1519686; hg19: chr6-114447123;