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GeneBe

9-92332277-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001012267.3(CENPP):c.215C>T(p.Thr72Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,612,096 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0031 ( 13 hom. )

Consequence

CENPP
NM_001012267.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0710
Variant links:
Genes affected
CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004699141).
BP6
Variant 9-92332277-C-T is Benign according to our data. Variant chr9-92332277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043563.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CENPPNM_001012267.3 linkuse as main transcriptc.215C>T p.Thr72Met missense_variant 2/8 ENST00000375587.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CENPPENST00000375587.8 linkuse as main transcriptc.215C>T p.Thr72Met missense_variant 2/81 NM_001012267.3 P1Q6IPU0-1

Frequencies

GnomAD3 genomes
AF:
0.00237
AC:
361
AN:
152056
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00128
Gnomad AMI
AF:
0.0263
Gnomad AMR
AF:
0.000983
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00371
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00216
AC:
539
AN:
249942
Hom.:
3
AF XY:
0.00216
AC XY:
292
AN XY:
135144
show subpopulations
Gnomad AFR exome
AF:
0.00130
Gnomad AMR exome
AF:
0.00129
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000461
Gnomad FIN exome
AF:
0.00157
Gnomad NFE exome
AF:
0.00359
Gnomad OTH exome
AF:
0.00313
GnomAD4 exome
AF:
0.00307
AC:
4480
AN:
1459922
Hom.:
13
Cov.:
30
AF XY:
0.00291
AC XY:
2113
AN XY:
726326
show subpopulations
Gnomad4 AFR exome
AF:
0.000749
Gnomad4 AMR exome
AF:
0.00141
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000384
Gnomad4 FIN exome
AF:
0.00187
Gnomad4 NFE exome
AF:
0.00371
Gnomad4 OTH exome
AF:
0.00221
GnomAD4 genome
AF:
0.00238
AC:
362
AN:
152174
Hom.:
1
Cov.:
33
AF XY:
0.00208
AC XY:
155
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00130
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.00371
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00304
Hom.:
3
Bravo
AF:
0.00217
TwinsUK
AF:
0.00405
AC:
15
ALSPAC
AF:
0.00337
AC:
13
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00360
AC:
31
ExAC
AF:
0.00250
AC:
303
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00262
EpiControl
AF:
0.00273

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CENPP-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 28, 2020This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
13
Dann
Benign
0.95
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.0047
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.088
Sift
Benign
0.12
T;.
Sift4G
Uncertain
0.031
D;T
Polyphen
0.27
B;.
Vest4
0.22
MVP
0.15
MPC
0.52
ClinPred
0.036
T
GERP RS
-3.4
Varity_R
0.014
gMVP
0.22

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: rs150818648; hg19: chr9-95094559; COSMIC: COSV100980993; API