6-114158356-T-G

Variant summary

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

The NM_153612.4(HS3ST5):c.-33+9995A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,110 control chromosomes in the GnomAD database, including 9,321 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 0.33 (9321 hom., cov: 33)
• Consequence: HS3ST5 NM_153612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST5	NM_153612.4	c.-33+9995A>C		intron_variant		ENST00000312719.10
HDAC2-AS2	NR_125845.1	n.1457-20297T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST5	ENST00000312719.10	c.-33+9995A>C		intron_variant		2	NM_153612.4	P1
HDAC2-AS2	ENST00000519104.5	n.1457-20297T>G		intron_variant, non_coding_transcript_variant		1
HDAC2-AS2	ENST00000523087.1	n.107-20669T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50965 AN: 151990 Hom.: 9332 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.335 AC: 50955 AN: 152110 Hom.: 9321 Cov.: 33 AF XY: 0.341 AC XY: 25329 AN XY: 74360

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.341

Alfa AF: 0.360 Hom.: 5168

Bravo AF: 0.341

Asia WGS AF: 0.472 AC: 1640 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.76

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: rs1889556; hg19: chr6-114479520;