rs1554747479
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_006096.4(NDRG1):c.1032_1091del(p.Thr350_Gly369del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000697 in 1,435,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
NDRG1
NM_006096.4 inframe_deletion
NM_006096.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.18
Genes affected
NDRG1 (HGNC:7679): (N-myc downstream regulated 1) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. The encoded protein is necessary for p53-mediated caspase activation and apoptosis. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4D, and expression of this gene may be a prognostic indicator for several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_006096.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDRG1 | NM_006096.4 | c.1032_1091del | p.Thr350_Gly369del | inframe_deletion | 16/16 | ENST00000323851.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDRG1 | ENST00000323851.13 | c.1032_1091del | p.Thr350_Gly369del | inframe_deletion | 16/16 | 1 | NM_006096.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1435572Hom.: 0 AF XY: 0.00000141 AC XY: 1AN XY: 711474
GnomAD4 exome
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711474
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2021 | This variant, c.1032_1091del, results in the deletion of 20 amino acid(s) of the NDRG1 protein (p.Thr350_Gly369del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NDRG1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at