17-13496169-AT-ATTT

Variant names:

• chr17-13496169-A-ATT
• rs67951062
• NM_006042.3:c.*26_*27dupAA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 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.*26_*27dupAA		3_prime_UTR	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.*26_*27dupAA		3_prime_UTR	Exon 2 of 2	ENSP00000284110.1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.*26_*27dupAA		splice_region	Exon 2 of 2	ENSP00000462696.1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.*26_*27dupAA		3_prime_UTR	Exon 2 of 2	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

GnomAD2 exomes AF: 0.368 AC: 57115 AN: 155092 AF XY: 0.370

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 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

African (AFR) AF: 0.219 AC: 5629 AN: 25704

American (AMR) AF: 0.497 AC: 13815 AN: 27776

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 7097 AN: 21216

East Asian (EAS) AF: 0.470 AC: 16382 AN: 34888

South Asian (SAS) AF: 0.501 AC: 32755 AN: 65370

European-Finnish (FIN) AF: 0.260 AC: 12649 AN: 48560

Middle Eastern (MID) AF: 0.354 AC: 1715 AN: 4846

European-Non Finnish (NFE) AF: 0.357 AC: 359950 AN: 1007406

Other (OTH) AF: 0.365 AC: 19219 AN: 52678

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

African (AFR) AF: 0.215 AC: 8844 AN: 41194

American (AMR) AF: 0.514 AC: 7797 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2849 AN: 5114

South Asian (SAS) AF: 0.587 AC: 2815 AN: 4798

European-Finnish (FIN) AF: 0.281 AC: 2865 AN: 10212

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.390 AC: 26414 AN: 67718

Other (OTH) AF: 0.373 AC: 779 AN: 2088

Alfa AF: 0.308 Hom.: 365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs67951062; hg19: chr17-13399486; COSMIC: COSV52372475; COSMIC: COSV52372475;