rs17055010

Variant names:

• chr4-169562149-C-T
• rs17055010
• NM_001199397.3:c.1068G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001199397.3(NEK1):​c.1068G>A​(p.Arg356Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0134 in 1,542,566 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (1273 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (1021 hom.)
• Consequence: NEK1 NM_001199397.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.09
• Publications: 3 publications found

Genes affected

NEK1 (HGNC:7744): (NIMA related kinase 1) The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

NEK1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis, susceptibility to, 24

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• short-rib thoracic dysplasia 6 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type II

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 4-169562149-C-T is Benign according to our data. Variant chr4-169562149-C-T is described in ClinVar as Benign. ClinVar VariationId is 348117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199397.3. 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
	NEK1	NM_001199397.3	MANE Select	c.1068G>A	p.Arg356Arg	synonymous	Exon 13 of 36	NP_001186326.1
	NEK1	NM_001374418.1		c.1068G>A	p.Arg356Arg	synonymous	Exon 12 of 35	NP_001361347.1
	NEK1	NM_001374419.1		c.1068G>A	p.Arg356Arg	synonymous	Exon 13 of 35	NP_001361348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK1	ENST00000507142.6	TSL:1 MANE Select	c.1068G>A	p.Arg356Arg	synonymous	Exon 13 of 36	ENSP00000424757.2
	NEK1	ENST00000439128.6	TSL:1	c.1068G>A	p.Arg356Arg	synonymous	Exon 12 of 34	ENSP00000408020.2
	NEK1	ENST00000511633.5	TSL:1	c.1068G>A	p.Arg356Arg	synonymous	Exon 13 of 35	ENSP00000423332.1

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10840 AN: 151812 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.0556

GnomAD2 exomes AF: 0.0151 AC: 2470 AN: 163598 AF XY: 0.0119

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.000116

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000922

Gnomad OTH exome AF: 0.00942

GnomAD4 exome AF: 0.00710 AC: 9870 AN: 1390636 Hom.: 1021 Cov.: 27 AF XY: 0.00623 AC XY: 4278 AN XY: 686598

African (AFR) AF: 0.246 AC: 7617 AN: 30916

American (AMR) AF: 0.0159 AC: 559 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25054

East Asian (EAS) AF: 0.00 AC: 0 AN: 36420

South Asian (SAS) AF: 0.000544 AC: 42 AN: 77244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49744

Middle Eastern (MID) AF: 0.0134 AC: 76 AN: 5674

European-Non Finnish (NFE) AF: 0.000592 AC: 635 AN: 1072718

Other (OTH) AF: 0.0163 AC: 940 AN: 57670

GnomAD4 genome AF: 0.0715 AC: 10858 AN: 151930 Hom.: 1273 Cov.: 32 AF XY: 0.0680 AC XY: 5055 AN XY: 74288

African (AFR) AF: 0.246 AC: 10193 AN: 41430

American (AMR) AF: 0.0305 AC: 465 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00102 AC: 69 AN: 67914

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0331 Hom.: 376

Bravo AF: 0.0819

Asia WGS AF: 0.0140 AC: 49 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Short-rib thoracic dysplasia 6 with or without polydactyly (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=96/4	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: rs17055010; hg19: chr4-170483300;