16-25692542-C-G

Variant names:

• chr16-25692542-C-G
• rs1285309025
• NM_006040.3:c.125C>G

Variant summary

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

The NM_006040.3(HS3ST4):​c.125C>G​(p.Ser42Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000767 in 1,304,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S42F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: HS3ST4 NM_006040.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• 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: 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=0.24558714).

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.125C>G	p.Ser42Cys	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.125C>G	p.Ser42Cys	missense	Exon 1 of 2	ENSP00000330606.5	Q9Y661
	ENSG00000310159	ENST00000847723.1		n.143+17G>C		intron	N/A
	ENSG00000310159	ENST00000847724.1		n.143+17G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1304454 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 643598

African (AFR) AF: 0.00 AC: 0 AN: 26418

American (AMR) AF: 0.00 AC: 0 AN: 29040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22090

East Asian (EAS) AF: 0.0000362 AC: 1 AN: 27592

South Asian (SAS) AF: 0.00 AC: 0 AN: 72868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026704

Other (OTH) AF: 0.00 AC: 0 AN: 52592

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0077	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.17
Sift	Benign	0.14	T
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.35
MutPred		0.35		Loss of sheet (P = 0.0457)
MVP		0.14
MPC		2.8
ClinPred		0.78	D
GERP RS		2.0
Varity_R		0.11
gMVP		0.39

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: rs1285309025; hg19: chr16-25703863;