1-198264132-A-G

Variant names:

• chr1-198264132-A-G
• rs753873003
• NM_133494.3:c.269A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_133494.3(NEK7):​c.269A>G​(p.Asn90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,585,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: NEK7 NM_133494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.66
• Publications: 0 publications found

Genes affected

NEK7 (HGNC:13386): (NIMA related kinase 7) NIMA-related kinases share high amino acid sequence identity with the gene product of the Aspergillus nidulans 'never in mitosis A' gene, which controls initiation of mitosis.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133494.3. 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
	NEK7	NM_133494.3	MANE Select	c.269A>G	p.Asn90Ser	missense	Exon 5 of 10	NP_598001.1	Q8TDX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK7	ENST00000367385.9	TSL:5 MANE Select	c.269A>G	p.Asn90Ser	missense	Exon 5 of 10	ENSP00000356355.4	Q8TDX7-1
	NEK7	ENST00000538004.5	TSL:1	c.269A>G	p.Asn90Ser	missense	Exon 5 of 10	ENSP00000444621.1	Q8TDX7-1
	NEK7	ENST00000961625.1		c.299A>G	p.Asn100Ser	missense	Exon 6 of 11	ENSP00000631684.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000854

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000620 AC: 14 AN: 225936 AF XY: 0.0000572

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000142

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000754

Gnomad OTH exome AF: 0.000185

GnomAD4 exome AF: 0.0000391 AC: 56 AN: 1433472 Hom.: 0 Cov.: 30 AF XY: 0.0000393 AC XY: 28 AN XY: 712080

African (AFR) AF: 0.00 AC: 0 AN: 31440

American (AMR) AF: 0.000206 AC: 8 AN: 38754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 38458

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.0000363 AC: 40 AN: 1101774

Other (OTH) AF: 0.000118 AC: 7 AN: 59274

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74240

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.000854 AC: 13 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		8.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.080	B
Vest4		0.62
MutPred		0.36		Loss of ubiquitination at K87 (P = 0.2053)
MVP		0.51
MPC		0.52
ClinPred		0.16	T
GERP RS		5.8
Varity_R		0.63
gMVP		0.45
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs753873003; hg19: chr1-198233262;