rs1060503092
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_006096.4(NDRG1):c.205+1G>T variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_006096.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDRG1 | NM_006096.4 | c.205+1G>T | splice_donor_variant | ENST00000323851.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDRG1 | ENST00000323851.13 | c.205+1G>T | splice_donor_variant | 1 | NM_006096.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461422Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727038
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2021 | This sequence change affects a donor splice site in intron 4 of the NDRG1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NDRG1 are known to be pathogenic (PMID: 12872253, 23996628). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neuropathy (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.