1-198278016-T-C

Position:

• chr1-198278016-T-C

Variant summary

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

The NM_133494.3(NEK7):​c.428T>C​(p.Val143Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK7 NM_133494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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	UniProt
NEK7	NM_133494.3	c.428T>C	p.Val143Ala	missense_variant	6/10	ENST00000367385.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK7	ENST00000367385.9	c.428T>C	p.Val143Ala	missense_variant	6/10	5	NM_133494.3	P1
NEK7	ENST00000538004.5	c.428T>C	p.Val143Ala	missense_variant	6/10	1		P1
NEK7	ENST00000493790.1	n.313T>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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 12, 2023

The c.428T>C (p.V143A) alteration is located in exon 6 (coding exon 5) of the NEK7 gene. This alteration results from a T to C substitution at nucleotide position 428, causing the valine (V) at amino acid position 143 to be replaced by an alanine (A). 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	Benign	0.30
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.24	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.23
Sift	Benign	0.14	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0060	B;B
Vest4		0.73
MutPred		0.55		Loss of MoRF binding (P = 0.14);Loss of MoRF binding (P = 0.14);
MVP		0.72
MPC		0.76
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.69
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-198247146;