chr3-131029889-A-G

Variant names:

• chr3-131029889-A-G
• rs9864242
• NM_024800.5:c.170+11A>G

Variant summary

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

The NM_024800.5(NEK11):​c.170+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,611,986 control chromosomes in the GnomAD database, including 128,319 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 0.31 (8873 hom., cov: 33)
  • Exomes 𝑓: 0.40 (119446 hom.)
• Consequence: NEK11 NM_024800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873

Genes affected

NEK11 (HGNC:18593): (NIMA related kinase 11) This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK11	NM_024800.5	c.170+11A>G		intron_variant	Intron 3 of 17	ENST00000383366.9	NP_079076.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9	c.170+11A>G		intron_variant	Intron 3 of 17	1	NM_024800.5	ENSP00000372857.4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46605 AN: 152036 Hom.: 8875 Cov.: 33

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.358 AC: 89788 AN: 251040 Hom.: 17287 AF XY: 0.365 AC XY: 49485 AN XY: 135722

Gnomad AFR exome AF: 0.0694

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.312

Gnomad FIN exome AF: 0.401

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.398 AC: 581606 AN: 1459832 Hom.: 119446 Cov.: 32 AF XY: 0.398 AC XY: 288994 AN XY: 726278

Gnomad4 AFR exome AF: 0.0689

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.306 AC: 46600 AN: 152154 Hom.: 8873 Cov.: 33 AF XY: 0.307 AC XY: 22807 AN XY: 74364

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.346

Alfa AF: 0.360 Hom.: 7382

Bravo AF: 0.295

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.8
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9864242; hg19: chr3-130748733; COSMIC: COSV53908845; COSMIC: COSV53908845;