rs61741326

Positions:

• chr17-13496299-A-C
• chr17-13496299-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006042.3(HS3ST3A1):​c.1119T>G​(p.Pro373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,382,272 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 27)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HS3ST3A1 NM_006042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.454 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.1119T>G	p.Pro373=	synonymous_variant	2/2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.522T>G	p.Pro174=	synonymous_variant	3/3		XP_011522416.1
HS3ST3A1	XM_047437228.1	c.522T>G	p.Pro174=	synonymous_variant	2/2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.1119T>G	p.Pro373=	synonymous_variant	2/2	1	NM_006042.3	ENSP00000284110	P1
HS3ST3A1	ENST00000578576.1	c.513T>G	p.Pro171=	synonymous_variant	2/2	3		ENSP00000462696

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000116 AC: 16 AN: 1382272 Hom.: 0 Cov.: 29 AF XY: 0.0000146 AC XY: 10 AN XY: 685212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000529

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000103

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.2
DANN	Benign	0.60

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: rs61741326; hg19: chr17-13399616;