17-13496299-A-T

Variant names:

• chr17-13496299-A-T
• rs61741326
• NM_006042.3:c.1119T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006042.3(HS3ST3A1):​c.1119T>A​(p.Pro373Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,529,094 control chromosomes in the GnomAD database, including 91,013 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 (8532 hom., cov: 27)
  • Exomes 𝑓: 0.36 (82481 hom.)
• Consequence: HS3ST3A1 NM_006042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.454 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.1119T>A	p.Pro373Pro	synonymous	Exon 2 of 2	NP_006033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.1119T>A	p.Pro373Pro	synonymous	Exon 2 of 2	ENSP00000284110.1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.513T>A	p.Pro171Pro	synonymous	Exon 2 of 2	ENSP00000462696.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 49246 AN: 148452 Hom.: 8521 Cov.: 27

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.385 AC: 78269 AN: 203314 AF XY: 0.387

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.512

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.363 AC: 501192 AN: 1380528 Hom.: 82481 Cov.: 29 AF XY: 0.365 AC XY: 250051 AN XY: 684314

African (AFR) AF: 0.203 AC: 6195 AN: 30478

American (AMR) AF: 0.536 AC: 16736 AN: 31238

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 7458 AN: 22792

East Asian (EAS) AF: 0.518 AC: 19944 AN: 38536

South Asian (SAS) AF: 0.491 AC: 37115 AN: 75522

European-Finnish (FIN) AF: 0.270 AC: 13948 AN: 51626

Middle Eastern (MID) AF: 0.353 AC: 1905 AN: 5400

European-Non Finnish (NFE) AF: 0.353 AC: 376991 AN: 1068086

Other (OTH) AF: 0.368 AC: 20900 AN: 56850

GnomAD4 genome AF: 0.332 AC: 49294 AN: 148566 Hom.: 8532 Cov.: 27 AF XY: 0.338 AC XY: 24487 AN XY: 72342

African (AFR) AF: 0.211 AC: 8652 AN: 40968

American (AMR) AF: 0.492 AC: 7274 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1129 AN: 3412

East Asian (EAS) AF: 0.531 AC: 2586 AN: 4872

South Asian (SAS) AF: 0.550 AC: 2452 AN: 4460

European-Finnish (FIN) AF: 0.283 AC: 2905 AN: 10266

Middle Eastern (MID) AF: 0.359 AC: 102 AN: 284

European-Non Finnish (NFE) AF: 0.348 AC: 23182 AN: 66576

Other (OTH) AF: 0.333 AC: 683 AN: 2050

Alfa AF: 0.229 Hom.: 683

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.45
Mutation Taster		=84/16	polymorphism (auto)

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: rs61741326; hg19: chr17-13399616; COSMIC: COSV52375136;