16-25692667-C-T

Variant names:

• chr16-25692667-C-T
• rs932202792
• NM_006040.3:c.250C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006040.3(HS3ST4):​c.250C>T​(p.Leu84Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HS3ST4 NM_006040.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 1 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.

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.250C>T	p.Leu84Leu	synonymous	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.250C>T	p.Leu84Leu	synonymous	Exon 1 of 2	ENSP00000330606.5	Q9Y661
	ENSG00000310159	ENST00000847723.1		n.35G>A		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000310159	ENST00000847724.1		n.35G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000174 AC: 1 AN: 57616 AF XY: 0.00

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1177428 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 575716

African (AFR) AF: 0.00 AC: 0 AN: 24382

American (AMR) AF: 0.00 AC: 0 AN: 20506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17846

East Asian (EAS) AF: 0.00 AC: 0 AN: 24430

South Asian (SAS) AF: 0.00 AC: 0 AN: 48768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 965310

Other (OTH) AF: 0.00 AC: 0 AN: 46230

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Uncertain	0.98
PhyloP100		1.3

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: rs932202792; hg19: chr16-25703988;