17-13496169-AT-ATTTT

Variant names:

• chr17-13496169-A-ATTT
• rs67951062
• NM_006042.3:c.*25_*27dupAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006042.3(HS3ST3A1):​c.*25_*27dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,416,560 control chromosomes in the GnomAD database, including 114 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 0)
  • Exomes 𝑓: 0.026 (95 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.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (2000/151064) while in subpopulation NFE AF = 0.02 (1354/67734). AF 95% confidence interval is 0.0191. There are 19 homozygotes in GnomAd4. There are 942 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.*25_*27dupAAA		3_prime_UTR_variant	Exon 2 of 2	ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.*25_*27dupAAA		3_prime_UTR_variant	Exon 3 of 3		XP_011522416.1
HS3ST3A1	XM_047437228.1	c.*25_*27dupAAA		3_prime_UTR_variant	Exon 2 of 2		XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.*25_*27dupAAA		3_prime_UTR_variant	Exon 2 of 2	1	NM_006042.3	ENSP00000284110.1
HS3ST3A1	ENST00000578576.1	c.*25_*27dupAAA		splice_region_variant	Exon 2 of 2	3		ENSP00000462696.1
HS3ST3A1	ENST00000578576.1	c.*25_*27dupAAA		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000462696.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1999 AN: 150960 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.00215

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.00966

GnomAD2 exomes AF: 0.0132 AC: 2048 AN: 155092 AF XY: 0.0130

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.00576

Gnomad EAS exome AF: 0.00628

Gnomad FIN exome AF: 0.0171

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.0256 AC: 32454 AN: 1265496 Hom.: 95 Cov.: 35 AF XY: 0.0251 AC XY: 15640 AN XY: 623626

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00452 AC: 119 AN: 26316

American (AMR) AF: 0.0209 AC: 559 AN: 26810

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 290 AN: 20960

East Asian (EAS) AF: 0.00596 AC: 197 AN: 33068

South Asian (SAS) AF: 0.0177 AC: 1125 AN: 63390

European-Finnish (FIN) AF: 0.0244 AC: 1177 AN: 48210

Middle Eastern (MID) AF: 0.00748 AC: 36 AN: 4816

European-Non Finnish (NFE) AF: 0.0281 AC: 27837 AN: 990308

Other (OTH) AF: 0.0216 AC: 1114 AN: 51618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0132 AC: 2000 AN: 151064 Hom.: 19 Cov.: 0 AF XY: 0.0128 AC XY: 942 AN XY: 73738

African (AFR) AF: 0.00429 AC: 177 AN: 41230

American (AMR) AF: 0.0110 AC: 167 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 22 AN: 3464

East Asian (EAS) AF: 0.00235 AC: 12 AN: 5116

South Asian (SAS) AF: 0.00292 AC: 14 AN: 4800

European-Finnish (FIN) AF: 0.0210 AC: 215 AN: 10246

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0200 AC: 1354 AN: 67734

Other (OTH) AF: 0.0100 AC: 21 AN: 2090

Alfa AF: 0.0140 Hom.: 365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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;