rs200947593

Variant names:

• chr16-1911802-C-A
• rs200947593
• NM_001009606.4:c.817G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1911802-C-A
• chr16-1911802-C-G
• chr16-1911802-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009606.4(HS3ST6):​c.817G>T​(p.Val273Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V273I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HS3ST6 NM_001009606.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596

Genes affected

HS3ST6 (HGNC:14178): (heparan sulfate-glucosamine 3-sulfotransferase 6) Predicted to enable [heparan sulfate]-glucosamine 3-sulfotransferase 1 activity. Predicted to be involved in glycosaminoglycan biosynthetic process. Predicted to act upstream of or within blastocyst hatching. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST6	NM_001009606.4	c.817G>T	p.Val273Phe	missense_variant	Exon 2 of 2	ENST00000454677.3	NP_001009606.3
HS3ST6	XM_011522608.3	c.442G>T	p.Val148Phe	missense_variant	Exon 2 of 2		XP_011520910.1
HS3ST6	XM_011522609.2	c.397G>T	p.Val133Phe	missense_variant	Exon 2 of 2		XP_011520911.1
HS3ST6	XM_047434487.1	c.397G>T	p.Val133Phe	missense_variant	Exon 2 of 2		XP_047290443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST6	ENST00000454677.3	c.817G>T	p.Val273Phe	missense_variant	Exon 2 of 2	1	NM_001009606.4	ENSP00000416741.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.092
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.30	N
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.072	D
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.63	T
REVEL	Uncertain	0.49
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.49		Loss of methylation at K276 (P = 0.109);
MVP		0.67
ClinPred		0.97	D
GERP RS		2.7
Varity_R		0.21
gMVP		0.66

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: rs200947593; hg19: chr16-1961803;