4-118053938-C-G

Position:

• chr4-118053938-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004784.3(NDST3):​c.28C>G​(p.His10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NDST3 NM_004784.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

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]

NDST3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST3	NM_004784.3	c.28C>G	p.His10Asp	missense_variant	2/14	ENST00000296499.6	NP_004775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.28C>G	p.His10Asp	missense_variant	2/14	1	NM_004784.3	ENSP00000296499.5
NDST3	ENST00000394488.2	n.477C>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.28C>G (p.H10D) alteration is located in exon 2 (coding exon 1) of the NDST3 gene. This alteration results from a C to G substitution at nucleotide position 28, causing the histidine (H) at amino acid position 10 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.093	T
Sift4G	Benign	0.35	T
Polyphen		0.073	B
Vest4		0.73
MutPred		0.40		Loss of MoRF binding (P = 0.0709);
MVP		0.69
MPC		1.6
ClinPred		0.67	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1725243392; hg19: chr4-118975093;