rs3809797

Variant names:

• chr17-28738193-T-C
• rs3809797
• NM_178170.3:c.1170T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-28738193-T-C
• chr17-28738193-T-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate 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
• Publications: 21 publications found

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]

NEK8 Gene-Disease associations (from GenCC):

• renal-hepatic-pancreatic dysplasia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• nephronophthisis 9

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• polycystic kidney disease 8

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal-hepatic-pancreatic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000265073 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.142).
• BP6: Variant 17-28738193-T-C is Benign according to our data. Variant chr17-28738193-T-C is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
NEK8	NM_178170.3	c.1170T>C	p.Gly390Gly	synonymous_variant	Exon 8 of 15	ENST00000268766.11	NP_835464.1

Ensembl

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

GnomAD2 exomes AF: 0.128 AC: 32057 AN: 251116 AF XY: 0.127

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 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

African (AFR) AF: 0.346 AC: 11580 AN: 33480

American (AMR) AF: 0.0788 AC: 3525 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3511 AN: 26134

East Asian (EAS) AF: 0.206 AC: 8192 AN: 39700

South Asian (SAS) AF: 0.208 AC: 17966 AN: 86252

European-Finnish (FIN) AF: 0.0841 AC: 4492 AN: 53416

Middle Eastern (MID) AF: 0.159 AC: 916 AN: 5764

European-Non Finnish (NFE) AF: 0.0884 AC: 98296 AN: 1111986

Other (OTH) AF: 0.120 AC: 7261 AN: 60392

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

African (AFR) AF: 0.323 AC: 13387 AN: 41446

American (AMR) AF: 0.116 AC: 1768 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.183 AC: 944 AN: 5154

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4826

European-Finnish (FIN) AF: 0.0843 AC: 894 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6060 AN: 67982

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.117 Hom.: 1560

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nephronophthisis 9 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Renal-hepatic-pancreatic dysplasia 2 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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