3-27256325-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.2061C>G(p.Thr687=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,559,310 control chromosomes in the GnomAD database, including 236,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (33074 hom., cov: 32)
  • Exomes 𝑓: 0.53 (203903 hom.)
• Consequence: NEK10 NM_001394966.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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=-0.71).
• BP6: Variant 3-27256325-G-C is Benign according to our data. Variant chr3-27256325-G-C is described in ClinVar as [Benign]. Clinvar id is 1325893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.2061C>G	p.Thr687=	synonymous_variant	23/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.2061C>G	p.Thr687=	synonymous_variant	23/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96514 AN: 151934 Hom.: 33012 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.626

GnomAD3 exomes AF: 0.531 AC: 114036 AN: 214942 Hom.: 32459 AF XY: 0.524 AC XY: 61421 AN XY: 117258

Gnomad AFR exome AF: 0.912

Gnomad AMR exome AF: 0.613

Gnomad ASJ exome AF: 0.552

Gnomad EAS exome AF: 0.199

Gnomad SAS exome AF: 0.482

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.523

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.530 AC: 746169 AN: 1407258 Hom.: 203903 Cov.: 28 AF XY: 0.528 AC XY: 369475 AN XY: 699918

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.636 AC: 96638 AN: 152052 Hom.: 33074 Cov.: 32 AF XY: 0.631 AC XY: 46900 AN XY: 74312

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.621

Alfa AF: 0.565 Hom.: 8214

Bravo AF: 0.656

Asia WGS AF: 0.449 AC: 1561 AN: 3474

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	-0.71
Cadd	Benign	0.22
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3213930; hg19: chr3-27297816; COSMIC: COSV58288478;