4-169562196-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001199397.3(NEK1):c.1021G>A(p.Ala341Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,527,934 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001199397.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00215 AC: 326AN: 151676Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00167 AC: 248AN: 148168Hom.: 0 AF XY: 0.00136 AC XY: 106AN XY: 78166
GnomAD4 exome AF: 0.00306 AC: 4217AN: 1376142Hom.: 8 Cov.: 27 AF XY: 0.00299 AC XY: 2028AN XY: 678660
GnomAD4 genome AF: 0.00215 AC: 326AN: 151792Hom.: 1 Cov.: 32 AF XY: 0.00214 AC XY: 159AN XY: 74158
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | NEK1: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2020 | This variant is associated with the following publications: (PMID: 28935222, 28089114, 30755392) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 12, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 21, 2024 | - - |
Short-rib thoracic dysplasia 6 with or without polydactyly Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2025 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 09, 2016 | - - |
Cough;C0021051:Immunodeficiency;C0024312:Lymphopenia;C0344697:Cor triatriatum dexter Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | - | - - |
Motor neuron disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Centre for Genomic and Experimental Medicine, University of Edinburgh | Aug 31, 2016 | - - |
NEK1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 28, 2022 | 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). - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at