rs141416529

Variant names:

• chr6-114058035-T-C
• rs141416529
• NM_153612.4:c.263A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153612.4(HS3ST5):​c.263A>G​(p.Gln88Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000436 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: HS3ST5 NM_153612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15624154).

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.263A>G	p.Gln88Arg	missense	Exon 5 of 5	NP_705840.2
	HS3ST5	NM_001387039.1		c.263A>G	p.Gln88Arg	missense	Exon 4 of 4	NP_001373968.1	Q8IZT8
	HS3ST5	NM_001387040.1		c.263A>G	p.Gln88Arg	missense	Exon 3 of 3	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.263A>G	p.Gln88Arg	missense	Exon 5 of 5	ENSP00000427888.1	Q8IZT8
	HDAC2-AS2	ENST00000519104.5	TSL:1	n.1311-30902T>C		intron	N/A
	HS3ST5	ENST00000900060.1		c.263A>G	p.Gln88Arg	missense	Exon 6 of 6	ENSP00000570119.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000255 AC: 64 AN: 251370 AF XY: 0.000155

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000445 AC: 651 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.000426 AC XY: 310 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000555 AC: 617 AN: 1112008

Other (OTH) AF: 0.000348 AC: 21 AN: 60396

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74370

African (AFR) AF: 0.0000482 AC: 2 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000385 Hom.: 0

Bravo AF: 0.000336

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		6.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.068
Sift	Benign	0.89	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.70
MVP		0.26
MPC		0.25
ClinPred		0.034	T
GERP RS		5.6
Varity_R		0.65
gMVP		0.62
Mutation Taster		=61/39	polymorphism

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: rs141416529; hg19: chr6-114379199;