chr9-124321795-C-T

Variant names:

• chr9-124321795-C-T
• rs2274782
• NM_014397.6:c.405+226C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEK6	NM_014397.6	c.405+226C>T		intron_variant	Intron 5 of 9	ENST00000320246.10	NP_055212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10	c.405+226C>T		intron_variant	Intron 5 of 9	1	NM_014397.6	ENSP00000319734.5

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

African (AFR) AF: 0.552 AC: 22922 AN: 41496

American (AMR) AF: 0.295 AC: 4512 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1610 AN: 5168

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3883 AN: 10580

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24200 AN: 67984

Other (OTH) AF: 0.357 AC: 756 AN: 2116

Alfa AF: 0.373 Hom.: 5413

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
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs2274782; hg19: chr9-127084074;