17-28729008-C-T

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+148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 726,040 control chromosomes in the GnomAD database, including 3,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (819 hom., cov: 33)
  • Exomes 𝑓: 0.095 (3062 hom.)
• Consequence: NEK8 NM_178170.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.504

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=-0.7).
• BP6: Variant 17-28729008-C-T is Benign according to our data. Variant chr17-28729008-C-T is described in ClinVar as [Benign]. Clinvar id is 1296813.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+148C>T		intron_variant		ENST00000268766.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK8	ENST00000268766.11	c.47+148C>T		intron_variant		1	NM_178170.3	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15398 AN: 152206 Hom.: 818 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0844

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: 0.0862

Gnomad OTH AF: 0.0989

GnomAD4 exome AF: 0.0951 AC: 54563 AN: 573716 Hom.: 3062 AF XY: 0.0972 AC XY: 29461 AN XY: 303210

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0649

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0774

Gnomad4 NFE exome AF: 0.0818

Gnomad4 OTH exome AF: 0.0930

GnomAD4 genome AF: 0.101 AC: 15402 AN: 152324 Hom.: 819 Cov.: 33 AF XY: 0.101 AC XY: 7543 AN XY: 74488

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.0983

Alfa AF: 0.0573 Hom.: 69

Bravo AF: 0.102

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	-0.70
Cadd	Benign	7.3
Dann	Benign	0.72

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: rs7211220; hg19: chr17-27056026; COSMIC: COSV52045569; COSMIC: COSV52045569;