NM_001543.5:c.730C>A

Variant names:

• chr5-150528020-C-A
• rs375092472
• NM_001543.5:c.730C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001543.5(NDST1):​c.730C>A​(p.Arg244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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: 2.23
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17528194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST1	NM_001543.5	c.730C>A	p.Arg244Ser	missense_variant	Exon 3 of 15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.730C>A	p.Arg244Ser	missense_variant	Exon 3 of 14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7	c.730C>A	p.Arg244Ser	missense_variant	Exon 3 of 15	1	NM_001543.5	ENSP00000261797.6
NDST1	ENST00000523767.5	c.730C>A	p.Arg244Ser	missense_variant	Exon 3 of 14	2		ENSP00000428604.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	.;N
PhyloP100		2.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Benign	0.13	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.047	B;B
Vest4		0.41
MutPred		0.27		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.27
MPC		1.1
ClinPred		0.38	T
GERP RS		4.1
Varity_R		0.19
gMVP		0.58
Mutation Taster		=72/28	polymorphism

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: rs375092472; hg19: chr5-149907582;