3-131029889-A-G

Variant names:

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

Variant summary

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

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK11	NM_024800.5	MANE Select	c.170+11A>G		intron	N/A	NP_079076.3
	NEK11	NM_001321221.2		c.170+11A>G		intron	N/A	NP_001308150.1
	NEK11	NM_001353022.2		c.170+11A>G		intron	N/A	NP_001339951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK11	ENST00000383366.9	TSL:1 MANE Select	c.170+11A>G		intron	N/A	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.170+11A>G		intron	N/A	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000507910.5	TSL:1	c.170+11A>G		intron	N/A	ENSP00000426662.1	Q8NG66-3

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

GnomAD2 exomes AF: 0.358 AC: 89788 AN: 251040 AF XY: 0.365

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 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

African (AFR) AF: 0.0689 AC: 2304 AN: 33452

American (AMR) AF: 0.372 AC: 16648 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8983 AN: 26108

East Asian (EAS) AF: 0.284 AC: 11275 AN: 39682

South Asian (SAS) AF: 0.318 AC: 27383 AN: 86210

European-Finnish (FIN) AF: 0.400 AC: 21325 AN: 53340

Middle Eastern (MID) AF: 0.487 AC: 2803 AN: 5760

European-Non Finnish (NFE) AF: 0.421 AC: 467870 AN: 1110228

Other (OTH) AF: 0.381 AC: 23015 AN: 60330

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

African (AFR) AF: 0.0756 AC: 3138 AN: 41524

American (AMR) AF: 0.374 AC: 5728 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3472

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5172

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4208 AN: 10566

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28457 AN: 67986

Other (OTH) AF: 0.346 AC: 731 AN: 2114

Alfa AF: 0.363 Hom.: 8011

Bravo AF: 0.295

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.8
DANN	Benign	0.71
PhyloP100		0.87
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9864242; hg19: chr3-130748733; COSMIC: COSV53908845; COSMIC: COSV53908845;