chr9-124351381-A-G

Variant names:

• chr9-124351381-A-G
• rs2416
• NM_014397.6:c.*434A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-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 rank	MANE	Protein	UniProt
NEK6	NM_014397.6	c.*434A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000320246.10	NP_055212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10	c.*434A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_014397.6	ENSP00000319734.5

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

African (AFR) AF: 0.311 AC: 59 AN: 190

American (AMR) AF: 0.476 AC: 263 AN: 552

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 124 AN: 232

East Asian (EAS) AF: 0.275 AC: 56 AN: 204

South Asian (SAS) AF: 0.343 AC: 285 AN: 830

European-Finnish (FIN) AF: 0.487 AC: 311 AN: 638

Middle Eastern (MID) AF: 0.583 AC: 21 AN: 36

European-Non Finnish (NFE) AF: 0.547 AC: 2997 AN: 5476

Other (OTH) AF: 0.507 AC: 310 AN: 612

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

African (AFR) AF: 0.355 AC: 14709 AN: 41470

American (AMR) AF: 0.512 AC: 7832 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1636 AN: 5166

South Asian (SAS) AF: 0.372 AC: 1790 AN: 4818

European-Finnish (FIN) AF: 0.522 AC: 5515 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38304 AN: 67988

Other (OTH) AF: 0.512 AC: 1083 AN: 2116

Alfa AF: 0.534 Hom.: 84632

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
PhyloP100		0.18
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: rs2416; hg19: chr9-127113660; COSMIC: COSV52333667; COSMIC: COSV52333667;