rs10510592

chr3-27291329-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394966.1(NEK10):c.1538T>C(p.Leu513Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,430 control chromosomes in the GnomAD database, including 53,151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4599 hom., cov: 33)
  • Exomes 𝑓: 0.25 (48552 hom.)
• Consequence: NEK10 NM_001394966.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.38

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003412515).
• BP6: Variant 3-27291329-A-G is Benign according to our data. Variant chr3-27291329-A-G is described in ClinVar as [Benign]. Clinvar id is 1325897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.1538T>C	p.Leu513Ser	missense_variant	18/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.1538T>C	p.Leu513Ser	missense_variant	18/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36037 AN: 152040 Hom.: 4598 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.268 AC: 66465 AN: 247720 Hom.: 9642 AF XY: 0.272 AC XY: 36544 AN XY: 134596

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.270

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.252 AC: 367581 AN: 1460272 Hom.: 48552 Cov.: 32 AF XY: 0.254 AC XY: 184709 AN XY: 726460

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.0908

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.237 AC: 36051 AN: 152158 Hom.: 4599 Cov.: 33 AF XY: 0.241 AC XY: 17931 AN XY: 74358

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.268

Alfa AF: 0.263 Hom.: 14349

Bravo AF: 0.237

TwinsUK AF: 0.255 AC: 944

ALSPAC AF: 0.238 AC: 919

ESP6500AA AF: 0.168 AC: 528

ESP6500EA AF: 0.270 AC: 1932

ExAC AF: 0.265 AC: 31829

Asia WGS AF: 0.185 AC: 645 AN: 3478

EpiCase AF: 0.284

EpiControl AF: 0.287

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2022

This variant is associated with the following publications: (PMID: 24943594) -

Ciliary dyskinesia, primary, 44 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	15
Dann	Benign	0.38
DEOGEN2	Benign	0.00073	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.023	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.72	T;T
Polyphen		0.0	B;.
Vest4		0.011
MPC		0.14
ClinPred		0.0018	T
GERP RS		2.8
Varity_R		0.037
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs10510592; hg19: chr3-27332820; COSMIC: COSV58284044; COSMIC: COSV58284044;