rs776534627

Variant names:

• chr6-114058146-C-T
• rs776534627
• NM_153612.4:c.152G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153612.4(HS3ST5):​c.152G>A​(p.Arg51His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,611,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: HS3ST5 NM_153612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04993221).

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.152G>A	p.Arg51His	missense	Exon 5 of 5	NP_705840.2
	HS3ST5	NM_001387039.1		c.152G>A	p.Arg51His	missense	Exon 4 of 4	NP_001373968.1	Q8IZT8
	HS3ST5	NM_001387040.1		c.152G>A	p.Arg51His	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.152G>A	p.Arg51His	missense	Exon 5 of 5	ENSP00000427888.1	Q8IZT8
	HDAC2-AS2	ENST00000519104.5	TSL:1	n.1311-30791C>T		intron	N/A
	HS3ST5	ENST00000900060.1		c.152G>A	p.Arg51His	missense	Exon 6 of 6	ENSP00000570119.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 249420 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1459404 Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21 AN XY: 725526

African (AFR) AF: 0.000209 AC: 7 AN: 33442

American (AMR) AF: 0.000112 AC: 5 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110164

Other (OTH) AF: 0.0000166 AC: 1 AN: 60280

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74328

African (AFR) AF: 0.000362 AC: 15 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000662 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

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	0.086
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.84
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.055
Sift	Benign	0.42	T
Sift4G	Benign	0.079	T
Polyphen		0.0	B
Vest4		0.069
MVP		0.093
MPC		0.27
ClinPred		0.014	T
GERP RS		3.0
Varity_R		0.025
gMVP		0.35
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776534627; hg19: chr6-114379310; COSMIC: COSV57137383;