17-13496169-AT-ATTT

Position:

• chr17-13496169-AT-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006042.3(HS3ST3A1):​c.*26_*27dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,439,400 control chromosomes in the GnomAD database, including 64,625 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10664 hom., cov: 0)
  • Exomes 𝑓: 0.36 (53961 hom.)
• Consequence: HS3ST3A1 NM_006042.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.*26_*27dupAA		3_prime_UTR_variant	2/2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.*26_*27dupAA		3_prime_UTR_variant	3/3		XP_011522416.1
HS3ST3A1	XM_047437228.1	c.*26_*27dupAA		3_prime_UTR_variant	2/2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110	c.*26_*27dupAA		3_prime_UTR_variant	2/2	1	NM_006042.3	ENSP00000284110.1
HS3ST3A1	ENST00000578576.1	c.*26_*27dupAA		splice_region_variant	2/2	3		ENSP00000462696.1
HS3ST3A1	ENST00000578576	c.*26_*27dupAA		3_prime_UTR_variant	2/2	3		ENSP00000462696.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54050 AN: 150854 Hom.: 10655 Cov.: 0

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.368 AC: 57115 AN: 155092 Hom.: 7710 AF XY: 0.370 AC XY: 31551 AN XY: 85292

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.364 AC: 469211 AN: 1288444 Hom.: 53961 Cov.: 35 AF XY: 0.367 AC XY: 233205 AN XY: 634988

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.358 AC: 54095 AN: 150956 Hom.: 10664 Cov.: 0 AF XY: 0.365 AC XY: 26884 AN XY: 73690

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs67951062; hg19: chr17-13399486;