4-118046041-A-G

Variant names:

• chr4-118046041-A-G
• rs6534079
• NM_004784.3:c.-155-7715A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004784.3(NDST3):​c.-155-7715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,472 control chromosomes in the GnomAD database, including 34,333 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 0.64 (34333 hom., cov: 28)
• Consequence: NDST3 NM_004784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST3	NM_004784.3	c.-155-7715A>G		intron_variant	Intron 1 of 13	ENST00000296499.6	NP_004775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.-155-7715A>G		intron_variant	Intron 1 of 13	1	NM_004784.3	ENSP00000296499.5
NDST3	ENST00000394488.2	n.295-7715A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 96797 AN: 151354 Hom.: 34315 Cov.: 28

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.639 AC: 96845 AN: 151472 Hom.: 34333 Cov.: 28 AF XY: 0.646 AC XY: 47793 AN XY: 73968

African (AFR) AF: 0.307 AC: 12668 AN: 41260

American (AMR) AF: 0.756 AC: 11468 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2616 AN: 3464

East Asian (EAS) AF: 0.748 AC: 3850 AN: 5150

South Asian (SAS) AF: 0.818 AC: 3872 AN: 4734

European-Finnish (FIN) AF: 0.783 AC: 8231 AN: 10510

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51911 AN: 67892

Other (OTH) AF: 0.642 AC: 1340 AN: 2086

Alfa AF: 0.688 Hom.: 7510

Bravo AF: 0.619

Asia WGS AF: 0.767 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs6534079; hg19: chr4-118967196;