chr4-118187620-G-T

Variant names:

• chr4-118187620-G-T
• rs6824418
• NM_004784.3:c.1540-36871G>T

Variant summary

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

The NM_004784.3(NDST3):​c.1540-36871G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,076 control chromosomes in the GnomAD database, including 607 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 0.062 (607 hom., cov: 32)
• Consequence: NDST3 NM_004784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 1 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]

ENSG00000297398 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST3	NM_004784.3	c.1540-36871G>T		intron_variant	Intron 6 of 13	ENST00000296499.6	NP_004775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.1540-36871G>T		intron_variant	Intron 6 of 13	1	NM_004784.3	ENSP00000296499.5
ENSG00000297398	ENST00000747715.1	n.405+16540C>A		intron_variant	Intron 4 of 7
ENSG00000297398	ENST00000747716.1	n.401+16540C>A		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9334 AN: 151958 Hom.: 601 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0494

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

GnomAD4 genome AF: 0.0616 AC: 9363 AN: 152076 Hom.: 607 Cov.: 32 AF XY: 0.0587 AC XY: 4367 AN XY: 74336

African (AFR) AF: 0.163 AC: 6766 AN: 41432

American (AMR) AF: 0.0273 AC: 417 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3468

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5170

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4824

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10590

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1663 AN: 68006

Other (OTH) AF: 0.0489 AC: 103 AN: 2108

Alfa AF: 0.0418 Hom.: 116

Bravo AF: 0.0671

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.25
DANN	Benign	0.16
PhyloP100		-1.5
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: rs6824418; hg19: chr4-119108775;