17-13496836-G-T

Position:

• chr17-13496836-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000284110.2(HS3ST3A1):​c.600-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,454,274 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: 30)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: HS3ST3A1 ENST00000284110.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3A1	NM_006042.3	c.600-18C>A		intron_variant		ENST00000284110.2	NP_006033.1
HS3ST3A1	XM_011524114.4	c.3-18C>A		intron_variant			XP_011522416.1
HS3ST3A1	XM_047437228.1	c.3-18C>A		intron_variant			XP_047293184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3A1	ENST00000284110.2	c.600-18C>A		intron_variant		1	NM_006042.3	ENSP00000284110	P1
HS3ST3A1	ENST00000578576.1	c.-7-18C>A		intron_variant		3		ENSP00000462696

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000963 AC: 14 AN: 1454274 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 8 AN XY: 722610

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.78

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: rs8080565; hg19: chr17-13400153;