rs3833163

Variant names:

• chr17-28740987-TGAG-T
• rs3833163
• NM_178170.3:c.1732+8_1732+10delGGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_178170.3(NEK8):​c.1732+8_1732+10delGGA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00304 in 1,614,112 control chromosomes in the GnomAD database, including 133 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (124 hom.)
• Consequence: NEK8 NM_178170.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.81
• Publications: 1 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: Ambry Genetics, ClinGen, G2P
• 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 -16 ACMG points.

• BP6: Variant 17-28740987-TGAG-T is Benign according to our data. Variant chr17-28740987-TGAG-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 242154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178170.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK8	NM_178170.3	MANE Select	c.1732+8_1732+10delGGA		splice_region intron	N/A	NP_835464.1	Q86SG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK8	ENST00000268766.11	TSL:1 MANE Select	c.1732+3_1732+5delGAG		splice_region intron	N/A	ENSP00000268766.6	Q86SG6
	NEK8	ENST00000969681.1		c.1771+3_1771+5delGAG		splice_region intron	N/A	ENSP00000639740.1
	NEK8	ENST00000903448.1		c.1600+3_1600+5delGAG		splice_region intron	N/A	ENSP00000573507.1

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 152142 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00831 AC: 2089 AN: 251356 AF XY: 0.00703

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0195

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.0690

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00299 AC: 4377 AN: 1461852 Hom.: 124 AF XY: 0.00292 AC XY: 2125 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0170 AC: 760 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26136

East Asian (EAS) AF: 0.0716 AC: 2844 AN: 39700

South Asian (SAS) AF: 0.00241 AC: 208 AN: 86258

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53390

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000256 AC: 285 AN: 1112000

Other (OTH) AF: 0.00381 AC: 230 AN: 60396

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152260 Hom.: 9 Cov.: 32 AF XY: 0.00398 AC XY: 296 AN XY: 74434

African (AFR) AF: 0.000289 AC: 12 AN: 41558

American (AMR) AF: 0.00621 AC: 95 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.0660 AC: 342 AN: 5178

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68016

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.00499

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Kidney disorder (1)
-	-	1	Nephronophthisis (1)
-	-	1	Nephronophthisis 9 (1)
-	-	1	Nephronophthisis 9;C3809434:Renal-hepatic-pancreatic dysplasia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8
Mutation Taster		=93/7	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: rs3833163; hg19: chr17-27068005; COSMIC: COSV99261560; COSMIC: COSV99261560;