rs2274782

Positions:

• chr9-124321795-C-T

Variant summary

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

The NM_014397.6(NEK6):​c.405+226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,126 control chromosomes in the GnomAD database, including 13,075 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 0.40 (13075 hom., cov: 34)
• Consequence: NEK6 NM_014397.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK6	NM_014397.6	c.405+226C>T		intron_variant		ENST00000320246.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK6	ENST00000320246.10	c.405+226C>T		intron_variant		1	NM_014397.6	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61250 AN: 152008 Hom.: 13069 Cov.: 34

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.362

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61289 AN: 152126 Hom.: 13075 Cov.: 34 AF XY: 0.401 AC XY: 29793 AN XY: 74368

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.357

Alfa AF: 0.374 Hom.: 4907

Bravo AF: 0.409

Asia WGS AF: 0.309 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.34

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: rs2274782; hg19: chr9-127084074;