3-27192007-C-A

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.2505+22G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,605,652 control chromosomes in the GnomAD database, including 51,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4366 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47184 hom.)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.591

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 (BayesDel_noAF=-0.86).
• BP6: Variant 3-27192007-C-A is Benign according to our data. Variant chr3-27192007-C-A is described in ClinVar as [Benign]. Clinvar id is 1325891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.2505+22G>T		intron_variant		ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.2505+22G>T		intron_variant			NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35217 AN: 151964 Hom.: 4365 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.266

GnomAD3 exomes AF: 0.262 AC: 65216 AN: 248576 Hom.: 9131 AF XY: 0.268 AC XY: 36048 AN XY: 134518

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.0910

Gnomad SAS exome AF: 0.314

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.249 AC: 361837 AN: 1453568 Hom.: 47184 Cov.: 29 AF XY: 0.252 AC XY: 182523 AN XY: 723698

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.0836

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.232 AC: 35229 AN: 152084 Hom.: 4366 Cov.: 32 AF XY: 0.236 AC XY: 17542 AN XY: 74340

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.263

Alfa AF: 0.255 Hom.: 1743

Bravo AF: 0.229

Asia WGS AF: 0.186 AC: 648 AN: 3478

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	-0.86
Cadd	Benign	3.7
Dann	Benign	0.55

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: rs11926556; hg19: chr3-27233498; COSMIC: COSV55357918;