5-150521415-C-G

Position:

chr5-150521415-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001543.5(NDST1):c.161C>G(p.Pro54Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NDST1
NM_001543.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15998155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST1	NM_001543.5 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/15	1	NM_001543.5	ENSP00000261797	P1	P52848-1
NDST1	ENST00000523767.5 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/14	2		ENSP00000428604		P52848-3
NDST1	ENST00000519157.1 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/2	5		ENSP00000427813
NDST1	ENST00000522491.1 linkuse as main transcript	c.161C>G	p.Pro54Arg	missense_variant	2/2	2		ENSP00000429966

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

247888

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000898

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1460854

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 24, 2021

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

.;.;.;T

Eigen

Benign

-0.043

Eigen_PC

Benign

0.042

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.60

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;.;.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

D;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.020

D;T;T;T

Sift4G

Uncertain

0.027

D;T;T;T

Polyphen

0.54, 0.17

.;.;P;B

Vest4

0.27, 0.26

MutPred

0.18

Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.30

MPC

0.89

ClinPred

0.21

GERP RS

5.1

Varity_R

0.10

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over