9-124351381-A-G

Position:

• chr9-124351381-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014397.6(NEK6):​c.*434A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 160,860 control chromosomes in the GnomAD database, including 19,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18494 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1222 hom.)
• Consequence: NEK6 NM_014397.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

Genes affected

NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK6	NM_014397.6	c.*434A>G		3_prime_UTR_variant	10/10	ENST00000320246.10	NP_055212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10	c.*434A>G		3_prime_UTR_variant	10/10	1	NM_014397.6	ENSP00000319734	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73428 AN: 151972 Hom.: 18490 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.505 AC: 4426 AN: 8770 Hom.: 1222 Cov.: 0 AF XY: 0.488 AC XY: 2214 AN XY: 4534

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.483 AC: 73451 AN: 152090 Hom.: 18494 Cov.: 33 AF XY: 0.478 AC XY: 35535 AN XY: 74322

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.512

Alfa AF: 0.548 Hom.: 37823

Bravo AF: 0.470

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.64

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: rs2416; hg19: chr9-127113660; COSMIC: COSV52333667; COSMIC: COSV52333667;