rs724244

Variant names:

• chr3-27200662-C-T
• rs724244
• NM_001394966.1:c.2291+848G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394966.1(NEK10):​c.2291+848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,074 control chromosomes in the GnomAD database, including 4,556 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 0.23 (4556 hom., cov: 32)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 5 publications found

Genes affected

NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

NEK10 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 44

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK10	NM_001394966.1	c.2291+848G>A		intron_variant	Intron 25 of 35	ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1	c.2291+848G>A		intron_variant	Intron 25 of 35		NM_001394966.1	ENSP00000509472.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35727 AN: 151952 Hom.: 4556 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.235 AC: 35736 AN: 152074 Hom.: 4556 Cov.: 32 AF XY: 0.240 AC XY: 17826 AN XY: 74322

African (AFR) AF: 0.141 AC: 5833 AN: 41478

American (AMR) AF: 0.317 AC: 4844 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3470

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5182

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3164 AN: 10548

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17863 AN: 67978

Other (OTH) AF: 0.267 AC: 564 AN: 2110

Alfa AF: 0.254 Hom.: 2400

Bravo AF: 0.230

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.54
PhyloP100		-1.5
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: rs724244; hg19: chr3-27242153;