16-25692737-G-A

Variant names:

• chr16-25692737-G-A
• rs930535665
• NM_006040.3:c.320G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006040.3(HS3ST4):​c.320G>A​(p.Ser107Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,282,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S107R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: HS3ST4 NM_006040.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

HS3ST4 (HGNC:5200): (heparan sulfate-glucosamine 3-sulfotransferase 4) This gene encodes the enzyme heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4. This enzyme generates 3-O-sulfated glucosaminyl residues in heparan sulfate. Cell surface heparan sulfate is used as a receptor by herpes simplex virus type 1 (HSV-1), and expression of this gene is thought to play a role in HSV-1 pathogenesis. [provided by RefSeq, Jul 2008]

ENSG00000310159 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09089893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006040.3. 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
	HS3ST4	NM_006040.3	MANE Select	c.320G>A	p.Ser107Asn	missense	Exon 1 of 2	NP_006031.2	Q9Y661

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST4	ENST00000331351.6	TSL:1 MANE Select	c.320G>A	p.Ser107Asn	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
	ENSG00000310159	ENST00000847723.1		n.-36C>T		upstream_gene	N/A
	ENSG00000310159	ENST00000847724.1		n.-36C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000378 AC: 57 AN: 150842 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000966

GnomAD4 exome AF: 0.0000362 AC: 41 AN: 1131566 Hom.: 0 Cov.: 31 AF XY: 0.0000384 AC XY: 21 AN XY: 546370

African (AFR) AF: 0.00157 AC: 36 AN: 22868

American (AMR) AF: 0.00 AC: 0 AN: 13024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15734

East Asian (EAS) AF: 0.00 AC: 0 AN: 25266

South Asian (SAS) AF: 0.00 AC: 0 AN: 31400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 951130

Other (OTH) AF: 0.000111 AC: 5 AN: 45154

GnomAD4 genome AF: 0.000378 AC: 57 AN: 150842 Hom.: 0 Cov.: 32 AF XY: 0.000380 AC XY: 28 AN XY: 73632

African (AFR) AF: 0.00126 AC: 52 AN: 41276

American (AMR) AF: 0.0000660 AC: 1 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5072

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67688

Other (OTH) AF: 0.000966 AC: 2 AN: 2070

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000416

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	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.084
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.21	T
Polyphen		0.37	B
Vest4		0.087
MVP		0.25
MPC		1.6
ClinPred		0.70	D
GERP RS		2.4
Varity_R		0.38
gMVP		0.13
Mutation Taster		=87/13	polymorphism

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: rs930535665; hg19: chr16-25704058;