17-28729007-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178170.3(NEK8):c.47+147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 726,114 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (868 hom., cov: 33)
  • Exomes 𝑓: 0.096 (3092 hom.)
• Consequence: NEK8 NM_178170.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.65

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-28729007-C-A is Benign according to our data. Variant chr17-28729007-C-A is described in ClinVar as [Benign]. Clinvar id is 1274047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK8	NM_178170.3	c.47+147C>A		intron_variant		ENST00000268766.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK8	ENST00000268766.11	c.47+147C>A		intron_variant		1	NM_178170.3	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15739 AN: 152202 Hom.: 866 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0959 AC: 55013 AN: 573794 Hom.: 3092 AF XY: 0.0979 AC XY: 29691 AN XY: 303278

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0661

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.0776

Gnomad4 NFE exome AF: 0.0823

Gnomad4 OTH exome AF: 0.0946

GnomAD4 genome AF: 0.103 AC: 15752 AN: 152320 Hom.: 868 Cov.: 33 AF XY: 0.103 AC XY: 7699 AN XY: 74476

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0344 Hom.: 19

Bravo AF: 0.105

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.0080
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7211214; hg19: chr17-27056025; COSMIC: COSV52047649; COSMIC: COSV52047649;