3-27201554-G-C

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.2247C>G(p.Val749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,611,470 control chromosomes in the GnomAD database, including 54,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4546 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49788 hom.)
• Consequence: NEK10 NM_001394966.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0330

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=-0.48).
• BP6: Variant 3-27201554-G-C is Benign according to our data. Variant chr3-27201554-G-C is described in ClinVar as [Benign]. Clinvar id is 1325892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.033 with no splicing effect.
• 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/exons	MANE	UniProt
NEK10	NM_001394966.1	c.2247C>G	p.Val749=	synonymous_variant	25/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.2247C>G	p.Val749=	synonymous_variant	25/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35716 AN: 151922 Hom.: 4546 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.266 AC: 66227 AN: 248608 Hom.: 9448 AF XY: 0.272 AC XY: 36614 AN XY: 134570

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.0883

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.255 AC: 372488 AN: 1459430 Hom.: 49788 Cov.: 32 AF XY: 0.258 AC XY: 187406 AN XY: 726072

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.0817

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.235 AC: 35724 AN: 152040 Hom.: 4546 Cov.: 32 AF XY: 0.240 AC XY: 17824 AN XY: 74306

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.269

Alfa AF: 0.260 Hom.: 1771

Bravo AF: 0.230

Asia WGS AF: 0.183 AC: 639 AN: 3478

EpiCase AF: 0.287

EpiControl AF: 0.290

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	6.7
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs17680166; hg19: chr3-27243045; COSMIC: COSV55358820;