3-27290686-T-C

Variant names:

• chr3-27290686-T-C
• rs674303
• NM_001394966.1:c.1674A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001394966.1(NEK10):​c.1674A>G​(p.Gly558Gly) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.197
• Publications: 14 publications found

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]

NEK10 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 44

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.003).
• BP6: Variant 3-27290686-T-C is Benign according to our data. Variant chr3-27290686-T-C is described in ClinVar as Benign. ClinVar VariationId is 1325896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394966.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	NM_001394966.1	MANE Select	c.1674A>G	p.Gly558Gly	synonymous	Exon 19 of 36	NP_001381895.1	A0A8I5KTB8
	NEK10	NM_001394970.1		c.1674A>G	p.Gly558Gly	synonymous	Exon 19 of 38	NP_001381899.1	Q6ZWH5-1
	NEK10	NM_152534.6		c.1674A>G	p.Gly558Gly	synonymous	Exon 20 of 39	NP_689747.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	ENST00000691995.1	MANE Select	c.1674A>G	p.Gly558Gly	synonymous	Exon 19 of 36	ENSP00000509472.1	A0A8I5KTB8
	NEK10	ENST00000429845.6	TSL:5	c.1674A>G	p.Gly558Gly	synonymous	Exon 20 of 39	ENSP00000395849.2	Q6ZWH5-1
	NEK10	ENST00000936071.1		c.1674A>G	p.Gly558Gly	synonymous	Exon 20 of 38	ENSP00000606130.1

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

GnomAD2 exomes AF: 0.277 AC: 68327 AN: 246924 AF XY: 0.266

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 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

African (AFR) AF: 0.772 AC: 25653 AN: 33232

American (AMR) AF: 0.256 AC: 11378 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6009 AN: 26034

East Asian (EAS) AF: 0.170 AC: 6729 AN: 39598

South Asian (SAS) AF: 0.205 AC: 17599 AN: 85646

European-Finnish (FIN) AF: 0.244 AC: 12965 AN: 53144

Middle Eastern (MID) AF: 0.253 AC: 1452 AN: 5750

European-Non Finnish (NFE) AF: 0.281 AC: 310483 AN: 1105912

Other (OTH) AF: 0.297 AC: 17881 AN: 60118

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

African (AFR) AF: 0.752 AC: 31208 AN: 41484

American (AMR) AF: 0.282 AC: 4310 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.167 AC: 863 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2779 AN: 10604

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18710 AN: 67970

Other (OTH) AF: 0.354 AC: 746 AN: 2110

Alfa AF: 0.315 Hom.: 6998

Bravo AF: 0.420

Asia WGS AF: 0.278 AC: 967 AN: 3474

EpiCase AF: 0.257

EpiControl AF: 0.266

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ciliary dyskinesia, primary, 44 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.1
DANN	Benign	0.75
PhyloP100		0.20
PromoterAI		-0.025	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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