1-198319446-A-T

Variant names:

• chr1-198319446-A-T
• NM_133494.3:c.833A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_133494.3(NEK7):​c.833A>T​(p.Asp278Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 6.67

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK7	NM_133494.3	c.833A>T	p.Asp278Val	missense_variant	Exon 10 of 10	ENST00000367385.9	NP_598001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK7	ENST00000367385.9	c.833A>T	p.Asp278Val	missense_variant	Exon 10 of 10	5	NM_133494.3	ENSP00000356355.4
NEK7	ENST00000538004.5	c.833A>T	p.Asp278Val	missense_variant	Exon 10 of 10	1		ENSP00000444621.1
NEK7	ENST00000493790.1	n.718A>T		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.833A>T (p.D278V) alteration is located in exon 10 (coding exon 9) of the NEK7 gene. This alteration results from a A to T substitution at nucleotide position 833, causing the aspartic acid (D) at amino acid position 278 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.80	P;P
Vest4		0.77
MutPred		0.68		Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);
MVP		0.74
MPC		1.7
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.84
gMVP		0.82

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: chr1-198288576;