rs1123418
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_017668.3(NDE1):c.744G>A(p.Ala248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000414 in 1,613,350 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 0 hom. )
Consequence
NDE1
NM_017668.3 synonymous
NM_017668.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.961
Genes affected
NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 16-15694205-G-A is Benign according to our data. Variant chr16-15694205-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159018.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.961 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000243 (37/152294) while in subpopulation NFE AF= 0.000397 (27/68026). AF 95% confidence interval is 0.00028. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDE1 | NM_017668.3 | c.744G>A | p.Ala248= | synonymous_variant | 7/9 | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDE1 | ENST00000396354.6 | c.744G>A | p.Ala248= | synonymous_variant | 7/9 | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250678Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135572
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GnomAD4 exome AF: 0.000432 AC: 631AN: 1461056Hom.: 0 Cov.: 32 AF XY: 0.000411 AC XY: 299AN XY: 726850
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74472
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2023 | - - |
Lissencephaly 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 04, 2013 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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