5-150521442-C-T

Position:

• chr5-150521442-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001543.5(NDST1):​c.188C>T​(p.Ala63Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NDST1. . Gene score misZ 2.9238 (greater than the threshold 3.09). Trascript score misZ 4.3135 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, intellectual disability, autosomal recessive 46.
• BP4: Computational evidence support a benign effect (MetaRNN=0.071556985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST1	NM_001543.5	c.188C>T	p.Ala63Val	missense_variant	2/15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.188C>T	p.Ala63Val	missense_variant	2/14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7	c.188C>T	p.Ala63Val	missense_variant	2/15	1	NM_001543.5	ENSP00000261797	P1
NDST1	ENST00000523767.5	c.188C>T	p.Ala63Val	missense_variant	2/14	2		ENSP00000428604
NDST1	ENST00000519157.1	c.188C>T	p.Ala63Val	missense_variant	2/2	5		ENSP00000427813
NDST1	ENST00000522491.1	c.188C>T	p.Ala63Val	missense_variant	2/2	2		ENSP00000429966

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2019

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek et al., 2016) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.16	.;.;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;.;N
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.065	T;T;T;T
Sift4G	Uncertain	0.034	D;T;T;T
Polyphen		0.014, 0.0030	.;.;B;B
Vest4		0.17, 0.13
MutPred		0.14		Gain of catalytic residue at A63 (P = 0.0652);Gain of catalytic residue at A63 (P = 0.0652);Gain of catalytic residue at A63 (P = 0.0652);Gain of catalytic residue at A63 (P = 0.0652);
MVP		0.37
MPC		0.66
ClinPred		0.12	T
GERP RS		4.2
Varity_R		0.042
gMVP		0.48

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: chr5-149901004;