1-163355367-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145697.3(NUF2):ā€‹c.1293G>Cā€‹(p.Glu431Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000935 in 1,604,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

NUF2
NM_145697.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51
Variant links:
Genes affected
NUF2 (HGNC:14621): (NUF2 component of NDC80 kinetochore complex) This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09552199).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUF2NM_145697.3 linkuse as main transcriptc.1293G>C p.Glu431Asp missense_variant 14/14 ENST00000271452.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUF2ENST00000271452.8 linkuse as main transcriptc.1293G>C p.Glu431Asp missense_variant 14/141 NM_145697.3 P1
NUF2ENST00000367900.7 linkuse as main transcriptc.1293G>C p.Glu431Asp missense_variant 14/141 P1
NUF2ENST00000524800.5 linkuse as main transcriptc.1152G>C p.Glu384Asp missense_variant 13/135

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
245954
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133164
show subpopulations
Gnomad AFR exome
AF:
0.000253
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000413
AC:
6
AN:
1452398
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
722584
show subpopulations
Gnomad4 AFR exome
AF:
0.000181
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 01, 2022The c.1293G>C (p.E431D) alteration is located in exon 14 (coding exon 13) of the NUF2 gene. This alteration results from a G to C substitution at nucleotide position 1293, causing the glutamic acid (E) at amino acid position 431 to be replaced by an aspartic acid (D). 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
0.17
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
.;T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.68
T;.;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.096
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
.;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.10
Sift
Benign
0.27
T;T;T
Sift4G
Benign
0.20
T;T;T
Polyphen
0.12
B;B;B
Vest4
0.14
MutPred
0.67
.;Loss of methylation at K432 (P = 0.0898);Loss of methylation at K432 (P = 0.0898);
MVP
0.42
MPC
0.34
ClinPred
0.11
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.067
gMVP
0.15

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146451154; hg19: chr1-163325157; API