5-150521397-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_001543.5(NDST1):ā€‹c.143C>Gā€‹(p.Ser48Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

NDST1
NM_001543.5 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 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=0.4035416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDST1NM_001543.5 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/15 ENST00000261797.7 NP_001534.1
NDST1NM_001301063.2 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/14 NP_001287992.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDST1ENST00000261797.7 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/151 NM_001543.5 ENSP00000261797 P1P52848-1
NDST1ENST00000523767.5 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/142 ENSP00000428604 P52848-3
NDST1ENST00000519157.1 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/25 ENSP00000427813
NDST1ENST00000522491.1 linkuse as main transcriptc.143C>G p.Ser48Trp missense_variant 2/22 ENSP00000429966

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460976
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726862
show subpopulations
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
AF:
0.00000657
AC:
1
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoNov 25, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
.;.;.;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.40
T;T;T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
1.8
.;.;.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-6.2
D;N;N;N
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;T;T;T
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0, 1.0
.;.;D;D
Vest4
0.58, 0.62
MutPred
0.30
Gain of catalytic residue at S48 (P = 5e-04);Gain of catalytic residue at S48 (P = 5e-04);Gain of catalytic residue at S48 (P = 5e-04);Gain of catalytic residue at S48 (P = 5e-04);
MVP
0.43
MPC
1.9
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.11
gMVP
0.47

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.

Other links and lift over

dbSNP: rs754000766; hg19: chr5-149900959; API