rs761957648

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001543.5(NDST1):​c.197G>A​(p.Arg66His) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,196 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

NDST1
NM_001543.5 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40368205).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDST1NM_001543.5 linkc.197G>A p.Arg66His missense_variant Exon 2 of 15 ENST00000261797.7 NP_001534.1 P52848-1A8K8T3
NDST1NM_001301063.2 linkc.197G>A p.Arg66His missense_variant Exon 2 of 14 NP_001287992.1 P52848-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDST1ENST00000261797.7 linkc.197G>A p.Arg66His missense_variant Exon 2 of 15 1 NM_001543.5 ENSP00000261797.6 P52848-1
NDST1ENST00000523767.5 linkc.197G>A p.Arg66His missense_variant Exon 2 of 14 2 ENSP00000428604.1 P52848-3
NDST1ENST00000519157.1 linkc.197G>A p.Arg66His missense_variant Exon 2 of 2 5 ENSP00000427813.1 E5RG58
NDST1ENST00000522491.1 linkc.197G>A p.Arg66His missense_variant Exon 2 of 2 2 ENSP00000429966.1 E5RGN9

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
248418
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134672
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1460990
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
726846
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000314
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Dec 03, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 66 of the NDST1 protein (p.Arg66His). This variant is present in population databases (rs761957648, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NDST1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2166526). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
.;.;.;T
Eigen
Benign
0.16
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.40
T;T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.1
.;.;.;M
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.6
D;N;N;N
REVEL
Benign
0.16
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;T;T
Polyphen
0.21, 0.10
.;.;B;B
Vest4
0.45, 0.45
MutPred
0.41
Gain of ubiquitination at K71 (P = 0.0317);Gain of ubiquitination at K71 (P = 0.0317);Gain of ubiquitination at K71 (P = 0.0317);Gain of ubiquitination at K71 (P = 0.0317);
MVP
0.73
MPC
0.86
ClinPred
0.65
D
GERP RS
5.1
Varity_R
0.31
gMVP
0.59

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: rs761957648; hg19: chr5-149901013; API