chr17-13600877-C-A

Position:

• chr17-13600877-C-A

Variant summary

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

The NM_006042.3(HS3ST3A1):​c.253G>T​(p.Ala85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,464,872 control chromosomes in the GnomAD database, including 458 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (67 hom., cov: 33)
  • Exomes 𝑓: 0.012 (391 hom.)
• Consequence: HS3ST3A1 NM_006042.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42

Genes affected

HS3ST3A1 (HGNC:5196): (heparan sulfate-glucosamine 3-sulfotransferase 3A1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. The sulfotransferase domain of this enzyme is highly similar to the same domain of heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3B1, and these two enzymes sulfate an identical disaccharide. This gene is widely expressed, with the most abundant expression in liver and placenta. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013333857).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST3A1	NM_006042.3	c.253G>T	p.Ala85Ser	missense_variant	1/2	ENST00000284110.2
HS3ST3A1	XM_017025480.3	c.253G>T	p.Ala85Ser	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.253G>T	p.Ala85Ser	missense_variant	1/2	1	NM_006042.3	P1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1812 AN: 152106 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00729

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0210 AC: 1319 AN: 62734 Hom.: 53 AF XY: 0.0222 AC XY: 800 AN XY: 36014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00552

Gnomad ASJ exome AF: 0.00273

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0483

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.00713

Gnomad OTH exome AF: 0.0166

GnomAD4 exome AF: 0.0123 AC: 16180 AN: 1312658 Hom.: 391 Cov.: 31 AF XY: 0.0132 AC XY: 8534 AN XY: 645752

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00431

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0457

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.00707

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0119 AC: 1811 AN: 152214 Hom.: 67 Cov.: 33 AF XY: 0.0132 AC XY: 984 AN XY: 74422

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.00729

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00321 Hom.: 0

Bravo AF: 0.00906

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00701 AC: 27

ExAC AF: 0.0175 AC: 359

Asia WGS AF: 0.0890 AC: 306 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	P
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.22	N
REVEL	Benign	0.076
Sift	Benign	0.56	T
Sift4G	Benign	0.86	T
Polyphen		0.42	B
Vest4		0.042
ClinPred		0.038	T
GERP RS		2.6
Varity_R		0.079
gMVP		0.34

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: rs60532842; hg19: chr17-13504194;