rs633398

Positions:

• chr4-118226308-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296499.6(NDST3):​c.1723-578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,070 control chromosomes in the GnomAD database, including 8,123 homozygotes. 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: 𝑓 0.29 (8123 hom., cov: 31)
• Consequence: NDST3 ENST00000296499.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

NDST3 (HGNC:7682): (N-deacetylase and N-sulfotransferase 3) This gene encodes a member of the heparan sulfate/heparin GlcNAc N-deacetylase/ N-sulfotransferase family. The encoded enzyme is a type II transmembrane protein that resides in the Golgi apparatus. This monomeric bifunctional enzyme catalyzes the N-deacetylation and N-sulfation of N-acetylglucosamine residues in heparan sulfate and heparin, which are the initial chemical modifications required for the biosynthesis of the functional oligosaccharide sequences that define the specific ligand binding activities of heparan sulfate and heparin. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST3	NM_004784.3	c.1723-578T>C		intron_variant		ENST00000296499.6	NP_004775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.1723-578T>C		intron_variant		1	NM_004784.3	ENSP00000296499	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44848 AN: 151952 Hom.: 8128 Cov.: 31

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44849 AN: 152070 Hom.: 8123 Cov.: 31 AF XY: 0.293 AC XY: 21779 AN XY: 74318

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.313

Alfa AF: 0.370 Hom.: 5086

Bravo AF: 0.290

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.54

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: rs633398; hg19: chr4-119147463;