4-118054354-C-T

Variant names:

• chr4-118054354-C-T
• NM_004784.3:c.444C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004784.3(NDST3):​c.444C>T​(p.Ser148Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NDST3 NM_004784.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=0.084 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST3	NM_004784.3	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 2 of 14	ENST00000296499.6	NP_004775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST3	ENST00000296499.6	c.444C>T	p.Ser148Ser	synonymous_variant	Exon 2 of 14	1	NM_004784.3	ENSP00000296499.5
NDST3	ENST00000394488.2	n.893C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460552 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.9
DANN	Benign	0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-118975509;