6-114108007-G-T

Position:

• chr6-114108007-G-T

Variant summary

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

The NM_153612.4(HS3ST5):​c.-32-45130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,946 control chromosomes in the GnomAD database, including 36,158 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 0.69 (36158 hom., cov: 31)
• Consequence: HS3ST5 NM_153612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST5	NM_153612.4	c.-32-45130C>A		intron_variant		ENST00000312719.10	NP_705840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST5	ENST00000312719.10	c.-32-45130C>A		intron_variant		2	NM_153612.4	ENSP00000427888.1
HDAC2-AS2	ENST00000519104.5	n.1394-8111G>T		intron_variant		1
HDAC2-AS2	ENST00000520034.5	n.139-8111G>T		intron_variant		3
HDAC2-AS2	ENST00000523087.1	n.107-71018G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104266 AN: 151828 Hom.: 36156 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.686 AC: 104300 AN: 151946 Hom.: 36158 Cov.: 31 AF XY: 0.689 AC XY: 51175 AN XY: 74272

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.701

Alfa AF: 0.684 Hom.: 6659

Bravo AF: 0.682

Asia WGS AF: 0.670 AC: 2324 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.89

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: rs1855625; hg19: chr6-114429171;