3-27284640-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394966.1(NEK10):c.1976A>G(p.Asn659Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00536 in 1,606,922 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (225 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (191 hom.)
• Consequence: NEK10 NM_001394966.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.67

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005199492).
• BP6: Variant 3-27284640-T-C is Benign according to our data. Variant chr3-27284640-T-C is described in ClinVar as [Benign]. Clinvar id is 778065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.1976A>G	p.Asn659Ser	missense_variant	22/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.1976A>G	p.Asn659Ser	missense_variant	22/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4435 AN: 152140 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00770 AC: 1935 AN: 251388 Hom.: 96 AF XY: 0.00570 AC XY: 775 AN XY: 135870

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00287 AC: 4181 AN: 1454664 Hom.: 191 Cov.: 29 AF XY: 0.00250 AC XY: 1812 AN XY: 724178

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00523

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000418

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000147

Gnomad4 OTH exome AF: 0.00612

GnomAD4 genome AF: 0.0291 AC: 4438 AN: 152258 Hom.: 225 Cov.: 32 AF XY: 0.0279 AC XY: 2074 AN XY: 74448

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00485 Hom.: 54

Bravo AF: 0.0333

ESP6500AA AF: 0.0908 AC: 400

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00950 AC: 1153

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0068	T;.
Eigen	Benign	0.085
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D
MetaRNN	Benign	0.0052	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.70	N;N
MutationTaster	Benign	0.0077	P;P;P
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.052	T;D
Polyphen		0.98	D;.
Vest4		0.42
MVP		0.50
MPC		0.27
ClinPred		0.024	T
GERP RS		6.0
Varity_R		0.42
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55833401; hg19: chr3-27326131;