3-27284606-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001394966.1(NEK10):c.2010C>A(p.Thr670=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,521,790 control chromosomes in the GnomAD database, including 47,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4578 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43358 hom.)
• Consequence: NEK10 NM_001394966.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.750

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-27284606-G-T is Benign according to our data. Variant chr3-27284606-G-T is described in ClinVar as [Benign]. Clinvar id is 1325894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.75 with no splicing effect.
• 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.2010C>A	p.Thr670=	synonymous_variant	22/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.2010C>A	p.Thr670=	synonymous_variant	22/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35967 AN: 151826 Hom.: 4577 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.268 AC: 67183 AN: 251110 Hom.: 9726 AF XY: 0.271 AC XY: 36803 AN XY: 135732

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.378

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.244 AC: 334610 AN: 1369846 Hom.: 43358 Cov.: 23 AF XY: 0.248 AC XY: 170032 AN XY: 686784

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.0893

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.237 AC: 35981 AN: 151944 Hom.: 4578 Cov.: 32 AF XY: 0.241 AC XY: 17909 AN XY: 74264

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.267

Alfa AF: 0.263 Hom.: 12458

Bravo AF: 0.237

Asia WGS AF: 0.184 AC: 643 AN: 3478

EpiCase AF: 0.283

EpiControl AF: 0.285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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
BayesDel_noAF	Benign	-0.50
Cadd	Benign	1.1
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs11129280; hg19: chr3-27326097; COSMIC: COSV58284017;