3-27290686-T-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.1674A>G(p.Gly558=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,606,012 control chromosomes in the GnomAD database, including 79,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (15810 hom., cov: 33)
  • Exomes 𝑓: 0.28 (63434 hom.)
• Consequence: NEK10 NM_001394966.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.197

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=-0.53).
• BP6: Variant 3-27290686-T-C is Benign according to our data. Variant chr3-27290686-T-C is described in ClinVar as [Benign]. Clinvar id is 1325896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.197 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1	c.1674A>G	p.Gly558=	synonymous_variant	19/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1	c.1674A>G	p.Gly558=	synonymous_variant	19/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60634 AN: 151998 Hom.: 15767 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.355

GnomAD3 exomes AF: 0.277 AC: 68327 AN: 246924 Hom.: 11732 AF XY: 0.266 AC XY: 35747 AN XY: 134184

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.282 AC: 410149 AN: 1453894 Hom.: 63434 Cov.: 27 AF XY: 0.277 AC XY: 200476 AN XY: 723658

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.399 AC: 60739 AN: 152118 Hom.: 15810 Cov.: 33 AF XY: 0.391 AC XY: 29046 AN XY: 74360

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.354

Alfa AF: 0.324 Hom.: 5623

Bravo AF: 0.420

Asia WGS AF: 0.278 AC: 967 AN: 3474

EpiCase AF: 0.257

EpiControl AF: 0.266

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	-0.53
Cadd	Benign	8.1
Dann	Benign	0.75

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: rs674303; hg19: chr3-27332177; COSMIC: COSV58280219;