rs552647

Positions:

• chr3-27312225-C-A
• chr3-27312225-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394966.1(NEK10):​c.490-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,134,696 control chromosomes in the GnomAD database, including 174,947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (33043 hom., cov: 32)
  • Exomes 𝑓: 0.53 (141904 hom.)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	Protein	UniProt
NEK10	NM_001394966.1	c.490-48G>T		intron_variant		ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1	c.490-48G>T		intron_variant			NM_001394966.1	ENSP00000509472	P1
NEK10	ENST00000341435.9	c.490-48G>T		intron_variant		2		ENSP00000343847
NEK10	ENST00000429845.6	c.490-48G>T		intron_variant		5		ENSP00000395849
NEK10	ENST00000491627.1	n.693-48G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96552 AN: 151974 Hom.: 32987 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.625

GnomAD3 exomes AF: 0.551 AC: 94206 AN: 170998 Hom.: 27270 AF XY: 0.543 AC XY: 50529 AN XY: 93026

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.245

Gnomad SAS exome AF: 0.504

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.527 AC: 517852 AN: 982604 Hom.: 141904 Cov.: 12 AF XY: 0.525 AC XY: 261732 AN XY: 498628

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.636 AC: 96668 AN: 152092 Hom.: 33043 Cov.: 32 AF XY: 0.631 AC XY: 46929 AN XY: 74338

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.620

Alfa AF: 0.550 Hom.: 39723

Bravo AF: 0.656

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.42

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: rs552647; hg19: chr3-27353716; COSMIC: COSV58283614;