chr17-13496598-T-C

Variant names:

• chr17-13496598-T-C
• rs759850617
• NM_006042.3:c.820A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006042.3(HS3ST3A1):​c.820A>G​(p.Arg274Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HS3ST3A1 NM_006042.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15890378).

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.820A>G	p.Arg274Gly	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.820A>G	p.Arg274Gly	missense	Exon 2 of 2	ENSP00000284110.1	Q9Y663
	HS3ST3A1	ENST00000578576.1	TSL:3	c.214A>G	p.Arg72Gly	missense	Exon 2 of 2	ENSP00000462696.1	J3KSX5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00 AC: 0 AN: 222984 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1457544 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725100

African (AFR) AF: 0.0000302 AC: 1 AN: 33078

American (AMR) AF: 0.00 AC: 0 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109502

Other (OTH) AF: 0.0000166 AC: 1 AN: 60166

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.18
BayesDel_addAF	Benign	-0.0014	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.90
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.30	N
PhyloP100		0.59
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.32
Sift	Benign	0.10	T
Sift4G	Benign	0.35	T
Polyphen		0.0020	B
Vest4		0.31
MutPred		0.55		Loss of helix (P = 0.0068)
MVP		0.040
ClinPred		0.12	T
GERP RS		-3.4
Varity_R		0.64
gMVP		0.48

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: rs759850617; hg19: chr17-13399915;