16-1911633-C-G

Variant names:

• chr16-1911633-C-G
• NM_001009606.4:c.986G>C

Variant summary

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

The NM_001009606.4(HS3ST6):​c.986G>C​(p.Arg329Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HS3ST6 NM_001009606.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916

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.986G>C	p.Arg329Pro	missense_variant	Exon 2 of 2	ENST00000454677.3	NP_001009606.3
HS3ST6	XM_011522608.3	c.611G>C	p.Arg204Pro	missense_variant	Exon 2 of 2		XP_011520910.1
HS3ST6	XM_011522609.2	c.566G>C	p.Arg189Pro	missense_variant	Exon 2 of 2		XP_011520911.1
HS3ST6	XM_047434487.1	c.566G>C	p.Arg189Pro	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.986G>C	p.Arg329Pro	missense_variant	Exon 2 of 2	1	NM_001009606.4	ENSP00000416741.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456176 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724112

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.32	T
REVEL	Benign	0.26
Sift4G	Benign	0.27	T
Polyphen		0.87	P
Vest4		0.39
MutPred		0.55		Loss of MoRF binding (P = 6e-04);
MVP		0.42
ClinPred		0.85	D
GERP RS		1.7
Varity_R		0.38
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1961634;