5-150528020-CGC-TCT

Variant names:

• chr5-150528020-CGC-TCT
• NM_001543.5:c.730_732delCGCinsTCT
• NDST1 p.Arg244Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001543.5(NDST1):​c.730_732delCGCinsTCT​(p.Arg244Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22
• Publications: 0 publications found

Genes affected

NDST1 (HGNC:7680): (N-deacetylase and N-sulfotransferase 1) 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. The encoded protein catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to nitrogen of glucosamine in heparan sulfate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

NDST1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 46

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001543.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST1	NM_001543.5	MANE Select	c.730_732delCGCinsTCT	p.Arg244Ser	missense	N/A	NP_001534.1	P52848-1
	NDST1	NM_001301063.2		c.730_732delCGCinsTCT	p.Arg244Ser	missense	N/A	NP_001287992.1	P52848-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST1	ENST00000261797.7	TSL:1 MANE Select	c.730_732delCGCinsTCT	p.Arg244Ser	missense	N/A	ENSP00000261797.6	P52848-1
	NDST1	ENST00000891672.1		c.730_732delCGCinsTCT	p.Arg244Ser	missense	N/A	ENSP00000561731.1
	NDST1	ENST00000965562.1		c.730_732delCGCinsTCT	p.Arg244Ser	missense	N/A	ENSP00000635621.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-149907582;