1-198319446-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

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. 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

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67
Variant links:
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]

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ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
NEK7NM_133494.3 linkuse as main transcriptc.833A>T p.Asp278Val missense_variant 10/10 ENST00000367385.9 NP_598001.1 Q8TDX7-1B2R8K8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEK7ENST00000367385.9 linkuse as main transcriptc.833A>T p.Asp278Val missense_variant 10/105 NM_133494.3 ENSP00000356355.4 Q8TDX7-1
NEK7ENST00000538004.5 linkuse as main transcriptc.833A>T p.Asp278Val missense_variant 10/101 ENSP00000444621.1 Q8TDX7-1
NEK7ENST00000493790.1 linkuse as main transcriptn.718A>T non_coding_transcript_exon_variant 5/52

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 11, 2024The 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; API