chr17-28738193-T-C

Position:

• chr17-28738193-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178170.3(NEK8):​c.1170T>C​(p.Gly390Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,942 control chromosomes in the GnomAD database, including 13,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2890 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10426 hom.)
• Consequence: NEK8 NM_178170.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.04

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]

ENSG00000265073 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-28738193-T-C is Benign according to our data. Variant chr17-28738193-T-C is described in ClinVar as [Benign]. Clinvar id is 262928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK8	NM_178170.3	c.1170T>C	p.Gly390Gly	synonymous_variant	8/15	ENST00000268766.11	NP_835464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK8	ENST00000268766.11	c.1170T>C	p.Gly390Gly	synonymous_variant	8/15	1	NM_178170.3	ENSP00000268766.6
NEK8	ENST00000592510.1	c.729T>C	p.Gly243Gly	synonymous_variant	5/5	3		ENSP00000466476.1
NEK8	ENST00000543014.1	n.1330T>C		non_coding_transcript_exon_variant	7/11	2		ENSP00000465859.1
ENSG00000265073	ENST00000584779.1	n.417+4156A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25000 AN: 151978 Hom.: 2885 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.128 AC: 32057 AN: 251116 Hom.: 2752 AF XY: 0.127 AC XY: 17255 AN XY: 135774

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.0744

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.0873

Gnomad NFE exome AF: 0.0888

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.107 AC: 155739 AN: 1461844 Hom.: 10426 Cov.: 35 AF XY: 0.109 AC XY: 79135 AN XY: 727222

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.0788

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.0841

Gnomad4 NFE exome AF: 0.0884

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.165 AC: 25034 AN: 152098 Hom.: 2890 Cov.: 33 AF XY: 0.165 AC XY: 12251 AN XY: 74364

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.142

Alfa AF: 0.119 Hom.: 1260

Bravo AF: 0.171

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Nephronophthisis 9 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Renal-hepatic-pancreatic dysplasia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3809797; hg19: chr17-27065211; COSMIC: COSV104392365; COSMIC: COSV104392365;