NM_006042.3:c.673G>T

Variant names:

• chr17-13496745-C-A
• rs1905293676
• NM_006042.3:c.673G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006042.3(HS3ST3A1):​c.673G>T​(p.Ala225Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: HS3ST3A1 NM_006042.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.673G>T	p.Ala225Ser	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.673G>T	p.Ala225Ser	missense	Exon 2 of 2	ENSP00000284110.1	Q9Y663
	HS3ST3A1	ENST00000578576.1	TSL:3	c.67G>T	p.Ala23Ser	missense	Exon 2 of 2	ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.91	P
Vest4		0.66
MutPred		0.66		Gain of phosphorylation at A225 (P = 0.009)
MVP		0.18
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.57

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: rs1905293676; hg19: chr17-13400062;