rs752878896
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001199397.3(NEK1):c.2814_2817delCAAA(p.Asn938LysfsTer53) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001199397.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249078Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135138
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461122Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 726870
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74336
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 6 with or without polydactyly Pathogenic:2
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not provided Pathogenic:1
The c.2730_2733delCAAA likely pathogenic variant in the NEK1 gene has been published in association with short-rib polydactyly syndrome type II also known as Majewski Syndrome (Zhang et al., 2017). It is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2730_2733delCAAA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at