chr5-150521493-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001543.5(NDST1):c.239G>A(p.Arg80His) variant causes a missense change. The variant allele was found at a frequency of 0.00211 in 1,613,898 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001543.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDST1 | ENST00000261797.7 | c.239G>A | p.Arg80His | missense_variant | Exon 2 of 15 | 1 | NM_001543.5 | ENSP00000261797.6 | ||
NDST1 | ENST00000523767.5 | c.239G>A | p.Arg80His | missense_variant | Exon 2 of 14 | 2 | ENSP00000428604.1 | |||
NDST1 | ENST00000519157.1 | c.239G>A | p.Arg80His | missense_variant | Exon 2 of 2 | 5 | ENSP00000427813.1 | |||
NDST1 | ENST00000522491.1 | c.*35G>A | downstream_gene_variant | 2 | ENSP00000429966.1 |
Frequencies
GnomAD3 genomes AF: 0.00137 AC: 209AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00108 AC: 271AN: 251066Hom.: 1 AF XY: 0.00106 AC XY: 144AN XY: 135754
GnomAD4 exome AF: 0.00219 AC: 3196AN: 1461658Hom.: 4 Cov.: 31 AF XY: 0.00211 AC XY: 1531AN XY: 727138
GnomAD4 genome AF: 0.00137 AC: 209AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
NDST1: BS2 -
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28211985, 30508070, 29178990, 25125150, 21937992, 14605369, 11457867) -
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not specified Uncertain:1
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Inborn genetic diseases Uncertain:1
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Intellectual disability, autosomal recessive 46 Uncertain:1
This 5-year old male with a history of global developmental delay, hyperkinesis, and mixed receptive-expressive language disorder was found to be compound heterozygous for two variants in the NDST1 gene. This variant is present in population databases at a frequency of 0.09% overall in ExAC and 0.11% in gnomAD. One homozygous individual was reported in gnomAD in an individual of non-Finnish European descent. Computational models predict this variant to be probably damaging to protein structure and/or function. This variant is located in the heparan sulfate N-deacetylase 1 domain of the protein. -
NDST1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Intellectual disability Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at