rs631271

Positions:

• chr4-118254749-G-A
• chr4-118254749-G-T

Variant summary

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

The NM_004784.3(NDST3):​c.2503-844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,964 control chromosomes in the GnomAD database, including 8,216 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 0.30 (8216 hom., cov: 32)
• Consequence: NDST3 NM_004784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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]

LOC105377392 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.2503-844G>A		intron_variant		ENST00000296499.6	NP_004775.1
LOC105377392	XR_939113.3	n.351-3062C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.2503-844G>A		intron_variant		1	NM_004784.3	ENSP00000296499	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45581 AN: 151848 Hom.: 8220 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.300 AC: 45591 AN: 151964 Hom.: 8216 Cov.: 32 AF XY: 0.298 AC XY: 22118 AN XY: 74254

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.320

Alfa AF: 0.376 Hom.: 14516

Bravo AF: 0.295

Asia WGS AF: 0.273 AC: 949 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.22

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: rs631271; hg19: chr4-119175904;