rs770321077

Variant names:

• chr6-114057609-C-G
• rs770321077
• NM_153612.4:c.689G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_153612.4(HS3ST5):​c.689G>C​(p.Arg230Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: HS3ST5 NM_153612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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.689G>C	p.Arg230Thr	missense	Exon 5 of 5	NP_705840.2
	HS3ST5	NM_001387039.1		c.689G>C	p.Arg230Thr	missense	Exon 4 of 4	NP_001373968.1	Q8IZT8
	HS3ST5	NM_001387040.1		c.689G>C	p.Arg230Thr	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.689G>C	p.Arg230Thr	missense	Exon 5 of 5	ENSP00000427888.1	Q8IZT8
	HDAC2-AS2	ENST00000519104.5	TSL:1	n.1311-31328C>G		intron	N/A
	HS3ST5	ENST00000900060.1		c.689G>C	p.Arg230Thr	missense	Exon 6 of 6	ENSP00000570119.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151366 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000977

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251210 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000815

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151366 Hom.: 0 Cov.: 32 AF XY: 0.0000406 AC XY: 3 AN XY: 73932

African (AFR) AF: 0.00 AC: 0 AN: 41120

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.000977 AC: 5 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67786

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000576 AC: 7

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Benign	0.91
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.71	N
PhyloP100		5.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.54
Sift	Benign	0.051	T
Sift4G	Benign	0.10	T
Polyphen		0.86	P
Vest4		0.75
MutPred		0.47		Loss of MoRF binding (P = 0.0152)
MVP		0.54
MPC		0.49
ClinPred		0.14	T
GERP RS		5.9
Varity_R		0.50
gMVP		0.86
Mutation Taster		=43/57	disease causing

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: rs770321077; hg19: chr6-114378773;