rs201629139
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1
The NM_178170.3(NEK8):c.1299+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,611,718 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00081 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000084 ( 2 hom. )
Consequence
NEK8
NM_178170.3 splice_donor_region, intron
NM_178170.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.08211
2
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
NEK8 (HGNC:13387): (NIMA related kinase 8) This gene encodes a member of the serine/threionine protein kinase family related to NIMA (never in mitosis, gene A) of Aspergillus nidulans. The encoded protein may play a role in cell cycle progression from G2 to M phase. Mutations in the related mouse gene are associated with a disease phenotype that closely parallels the juvenile autosomal recessive form of polycystic kidney disease in humans. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 17-28738750-G-T is Benign according to our data. Variant chr17-28738750-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 539139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000814 (124/152356) while in subpopulation AFR AF= 0.00291 (121/41586). AF 95% confidence interval is 0.00249. There are 1 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEK8 | NM_178170.3 | c.1299+3G>T | splice_donor_region_variant, intron_variant | ENST00000268766.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEK8 | ENST00000268766.11 | c.1299+3G>T | splice_donor_region_variant, intron_variant | 1 | NM_178170.3 | P1 | |||
ENST00000584779.1 | n.417+3599C>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
NEK8 | ENST00000543014.1 | c.*76+3G>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000808 AC: 123AN: 152238Hom.: 1 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
123
AN:
152238
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251300Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135836
GnomAD3 exomes
AF:
AC:
53
AN:
251300
Hom.:
AF XY:
AC XY:
16
AN XY:
135836
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000836 AC: 122AN: 1459362Hom.: 2 Cov.: 31 AF XY: 0.0000661 AC XY: 48AN XY: 726198
GnomAD4 exome
AF:
AC:
122
AN:
1459362
Hom.:
Cov.:
31
AF XY:
AC XY:
48
AN XY:
726198
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000814 AC: 124AN: 152356Hom.: 1 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74500
GnomAD4 genome
?
AF:
AC:
124
AN:
152356
Hom.:
Cov.:
33
AF XY:
AC XY:
56
AN XY:
74500
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
NEK8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 25, 2019 | 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). - |
Nephronophthisis 9;C3809434:Renal-hepatic-pancreatic dysplasia 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 05, 2022 | - - |
Nephronophthisis 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at