5-150521397-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001543.5(NDST1):āc.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
NM_001543.5 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 4.99
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]
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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 |
---|---|---|---|---|---|---|---|---|
NDST1 | NM_001543.5 | c.143C>G | p.Ser48Trp | missense_variant | 2/15 | ENST00000261797.7 | NP_001534.1 | |
NDST1 | NM_001301063.2 | c.143C>G | p.Ser48Trp | missense_variant | 2/14 | NP_001287992.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDST1 | ENST00000261797.7 | c.143C>G | p.Ser48Trp | missense_variant | 2/15 | 1 | NM_001543.5 | ENSP00000261797 | P1 | |
NDST1 | ENST00000523767.5 | c.143C>G | p.Ser48Trp | missense_variant | 2/14 | 2 | ENSP00000428604 | |||
NDST1 | ENST00000519157.1 | c.143C>G | p.Ser48Trp | missense_variant | 2/2 | 5 | ENSP00000427813 | |||
NDST1 | ENST00000522491.1 | c.143C>G | p.Ser48Trp | missense_variant | 2/2 | 2 | ENSP00000429966 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460976Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726862
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74330
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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 submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 25, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;N;N;N
REVEL
Benign
Sift
Pathogenic
D;T;T;T
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0, 1.0
.;.;D;D
Vest4
0.58, 0.62
MutPred
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
MPC
1.9
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at