NM_001394966.1:c.2505+22G>T

Variant names:

• chr3-27192007-C-A
• rs11926556
• NM_001394966.1:c.2505+22G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.591
• Publications: 3 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 -20 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 VariationId is 1325891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 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.2505+22G>T		intron	N/A	NP_001381895.1	A0A8I5KTB8
	NEK10	NM_001394970.1		c.2505+22G>T		intron	N/A	NP_001381899.1	Q6ZWH5-1
	NEK10	NM_152534.6		c.2505+22G>T		intron	N/A	NP_689747.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	ENST00000691995.1	MANE Select	c.2505+22G>T		intron	N/A	ENSP00000509472.1	A0A8I5KTB8
	NEK10	ENST00000383771.8	TSL:1	c.441+22G>T		intron	N/A	ENSP00000373281.4	Q6ZWH5-6
	NEK10	ENST00000429845.6	TSL:5	c.2505+22G>T		intron	N/A	ENSP00000395849.2	Q6ZWH5-1

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

GnomAD2 exomes AF: 0.262 AC: 65216 AN: 248576 AF XY: 0.268

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 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

African (AFR) AF: 0.146 AC: 4875 AN: 33300

American (AMR) AF: 0.338 AC: 15115 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 8571 AN: 26080

East Asian (EAS) AF: 0.0836 AC: 3314 AN: 39660

South Asian (SAS) AF: 0.312 AC: 26818 AN: 86072

European-Finnish (FIN) AF: 0.267 AC: 14267 AN: 53394

Middle Eastern (MID) AF: 0.392 AC: 2252 AN: 5752

European-Non Finnish (NFE) AF: 0.246 AC: 271630 AN: 1104482

Other (OTH) AF: 0.249 AC: 14995 AN: 60132

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

African (AFR) AF: 0.151 AC: 6251 AN: 41512

American (AMR) AF: 0.312 AC: 4766 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1143 AN: 3470

East Asian (EAS) AF: 0.0862 AC: 447 AN: 5186

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2837 AN: 10560

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.255 AC: 17315 AN: 67970

Other (OTH) AF: 0.263 AC: 555 AN: 2110

Alfa AF: 0.253 Hom.: 2698

Bravo AF: 0.229

Asia WGS AF: 0.186 AC: 648 AN: 3478

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	-0.86
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		0.59
Mutation Taster		=100/0	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: rs11926556; hg19: chr3-27233498; COSMIC: COSV55357918;