1-214646922-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016343.4(CENPF):​c.7352A>T​(p.Asn2451Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2451S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

5 publications found
Variant links:
Genes affected
CENPF (HGNC:1857): (centromere protein F) This gene encodes a protein that associates with the centromere-kinetochore complex. The protein is a component of the nuclear matrix during the G2 phase of interphase. In late G2 the protein associates with the kinetochore and maintains this association through early anaphase. It localizes to the spindle midzone and the intracellular bridge in late anaphase and telophase, respectively, and is thought to be subsequently degraded. The localization of this protein suggests that it may play a role in chromosome segregation during mitotis. It is thought to form either a homodimer or heterodimer. Autoantibodies against this protein have been found in patients with cancer or graft versus host disease. [provided by RefSeq, Jul 2008]
CENPF Gene-Disease associations (from GenCC):
  • Stromme syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16485664).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPFNM_016343.4 linkc.7352A>T p.Asn2451Ile missense_variant Exon 13 of 20 ENST00000366955.8 NP_057427.3 P49454
CENPFXM_017000086.3 linkc.7352A>T p.Asn2451Ile missense_variant Exon 13 of 20 XP_016855575.1 P49454
CENPFXM_011509082.4 linkc.7352A>T p.Asn2451Ile missense_variant Exon 13 of 19 XP_011507384.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPFENST00000366955.8 linkc.7352A>T p.Asn2451Ile missense_variant Exon 13 of 20 1 NM_016343.4 ENSP00000355922.3 P49454
CENPFENST00000706765.1 linkc.7352A>T p.Asn2451Ile missense_variant Exon 13 of 19 ENSP00000516538.1 A0A9L9PXU7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461792
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111968
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
7.9
DANN
Benign
0.78
Eigen
Benign
-0.91
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.96
T
PhyloP100
0.14
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.085
Sift
Uncertain
0.026
D
Sift4G
Benign
0.10
T
Vest4
0.35
MVP
0.16
MPC
0.072
ClinPred
0.61
D
GERP RS
-5.9
Varity_R
0.13
gMVP
0.19
Mutation Taster
=94/6
polymorphism

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

Other links and lift over

dbSNP: rs138083875; hg19: chr1-214820265; API