chr1-198264178-T-G

Position:

• chr1-198264178-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133494.3(NEK7):​c.315T>G​(p.Asn105Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK7 NM_133494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.566

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK7	NM_133494.3	c.315T>G	p.Asn105Lys	missense_variant	5/10	ENST00000367385.9	NP_598001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK7	ENST00000367385.9	c.315T>G	p.Asn105Lys	missense_variant	5/10	5	NM_133494.3	ENSP00000356355.4
NEK7	ENST00000538004.5	c.315T>G	p.Asn105Lys	missense_variant	5/10	1		ENSP00000444621.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 18, 2024

The c.315T>G (p.N105K) alteration is located in exon 5 (coding exon 4) of the NEK7 gene. This alteration results from a T to G substitution at nucleotide position 315, causing the asparagine (N) at amino acid position 105 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.70	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Benign	0.12
Sift	Benign	0.078	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.49	P;P
Vest4		0.78
MutPred		0.55		Gain of methylation at N105 (P = 0.0126);Gain of methylation at N105 (P = 0.0126);
MVP		0.65
MPC		0.98
ClinPred		0.92	D
GERP RS		3.5
Varity_R		0.79
gMVP		0.73

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: rs1653573809; hg19: chr1-198233308;