17-13496265-C-T

Variant names:

• chr17-13496265-C-T
• rs759045831
• NM_006042.3:c.1153G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006042.3(HS3ST3A1):​c.1153G>A​(p.Glu385Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E385Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: HS3ST3A1 NM_006042.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2949164).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	NM_006042.3	MANE Select	c.1153G>A	p.Glu385Lys	missense	Exon 2 of 2	NP_006033.1	Q9Y663

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3A1	ENST00000284110.2	TSL:1 MANE Select	c.1153G>A	p.Glu385Lys	missense	Exon 2 of 2	ENSP00000284110.1	Q9Y663
	HS3ST3A1	ENST00000578576.1	TSL:3	c.547G>A	p.Glu183Lys	missense	Exon 2 of 2	ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.066
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.31
Sift	Benign	0.50	T
Sift4G	Benign	0.36	T
Polyphen		0.0060	B
Vest4		0.29
MutPred		0.53		Gain of methylation at E385 (P = 0.0019)
MVP		0.16
ClinPred		0.76	D
GERP RS		5.2
Varity_R		0.50
gMVP		0.42

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: rs759045831; hg19: chr17-13399582;