17-28738193-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_178170.3(NEK8):​c.1170T>G​(p.Gly390Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G390G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK8 NM_178170.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.139).
• BP7: Synonymous conserved (PhyloP=-3.04 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-3.0

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;