NM_006042.3:c.600-18C>A

Variant names:

• chr17-13496836-G-T
• rs8080565
• NM_006042.3:c.600-18C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006042.3(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 NM_006042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

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

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.600-18C>A		intron	N/A	NP_006033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.600-18C>A		intron	N/A	ENSP00000284110.1
	HS3ST3A1	ENST00000578576.1	TSL:3	c.-7-18C>A		intron	N/A	ENSP00000462696.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25362

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 84844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1107856

Other (OTH) AF: 0.00 AC: 0 AN: 60028

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 608

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.78
PhyloP100		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

Other links and lift over

dbSNP: rs8080565; hg19: chr17-13400153;