rs373858942

Variant names:

• chr16-1911952-C-A
• rs373858942
• NM_001009606.4:c.667G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1911952-C-A
• chr16-1911952-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001009606.4(HS3ST6):​c.667G>T​(p.Val223Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HS3ST6 NM_001009606.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST6	NM_001009606.4	c.667G>T	p.Val223Phe	missense_variant	Exon 2 of 2	ENST00000454677.3	NP_001009606.3
HS3ST6	XM_011522608.3	c.292G>T	p.Val98Phe	missense_variant	Exon 2 of 2		XP_011520910.1
HS3ST6	XM_011522609.2	c.247G>T	p.Val83Phe	missense_variant	Exon 2 of 2		XP_011520911.1
HS3ST6	XM_047434487.1	c.247G>T	p.Val83Phe	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.667G>T	p.Val223Phe	missense_variant	Exon 2 of 2	1	NM_001009606.4	ENSP00000416741.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426284 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 705318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.75	T
REVEL	Uncertain	0.30
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.70		Gain of catalytic residue at V223 (P = 0.0571);
MVP		0.57
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.59
gMVP		0.78

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: rs373858942; hg19: chr16-1961953;