17-28741960-G-C

Variant names:

• chr17-28741960-G-C
• rs145898152
• NM_178170.3:c.2052G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_178170.3(NEK8):​c.2052G>C​(p.Ser684Ser) variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S684S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK8 NM_178170.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00002398
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -10.2

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=-10.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK8	NM_178170.3	c.2052G>C	p.Ser684Ser	splice_region_variant, synonymous_variant	Exon 15 of 15	ENST00000268766.11	NP_835464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK8	ENST00000268766.11	c.2052G>C	p.Ser684Ser	splice_region_variant, synonymous_variant	Exon 15 of 15	1	NM_178170.3	ENSP00000268766.6
NEK8	ENST00000543014.1	n.*193G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000465859.1
NEK8	ENST00000543014.1	n.*193G>C		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000465859.1
ENSG00000265073	ENST00000584779.1	n.417+389C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.016
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: rs145898152; hg19: chr17-27068978;