chrX-101102345-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001386188.2(CENPI):c.298T>C(p.Trp100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,188,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000017 ( 0 hom. 7 hem. )

Consequence

CENPI
NM_001386188.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Publications

0 publications found

Variant links:

Genes affected

CENPI (HGNC:3968): (centromere protein I) This gene encodes a centromere protein that is a component of the CENPA-NAC (nucleosome-associated) complex. This complex is critical for accurate chromosome alignment and segregation and it ensures proper mitotic progression. This protein regulates the recruitment of kinetochore-associated proteins that are required to generate the spindle checkpoint signal. The product of this gene is involved in the response of gonadal tissues to follicle-stimulating hormone. Mutations in this gene may be involved in human X-linked disorders of gonadal development and gametogenesis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 13. [provided by RefSeq, Jan 2016]

CENPI Gene-Disease associations (from GenCC):

idiopathic steroid-sensitive nephrotic syndrome
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CENPI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23831636).

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386188.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPI	NM_001386188.2	MANE Select	c.298T>C	p.Trp100Arg	missense	Exon 4 of 22	NP_001373117.1	Q92674-1
CENPI	NM_006733.3		c.298T>C	p.Trp100Arg	missense	Exon 3 of 21	NP_006724.2	Q92674-1
CENPI	NM_001318521.2		c.298T>C	p.Trp100Arg	missense	Exon 4 of 21	NP_001305450.1	A0A8C8KX99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPI	ENST00000682095.1	MANE Select	c.298T>C	p.Trp100Arg	missense	Exon 4 of 22	ENSP00000507927.1	Q92674-1
CENPI	ENST00000372927.5	TSL:5	c.298T>C	p.Trp100Arg	missense	Exon 3 of 21	ENSP00000362018.1	Q92674-1
CENPI	ENST00000684367.1		c.298T>C	p.Trp100Arg	missense	Exon 5 of 23	ENSP00000507595.1	Q92674-1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111417

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

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

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

177470

AF XY:

0.0000161

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1077112

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

343700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25962

American (AMR)

AF:

0.0000288

AC:

AN:

34725

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19160

East Asian (EAS)

AF:

0.00

AC:

AN:

29976

South Asian (SAS)

AF:

0.00

AC:

AN:

52542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40401

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.0000206

AC:

AN:

824963

Other (OTH)

AF:

0.00

AC:

AN:

45339

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111417

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33577

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30738

American (AMR)

AF:

0.000194

AC:

AN:

10335

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3597

South Asian (SAS)

AF:

0.00

AC:

AN:

2677

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53159

Other (OTH)

AF:

0.00

AC:

AN:

1494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.073

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.59

M_CAP

Benign

0.0056

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

PhyloP100

2.3

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.13

Sift

Benign

0.49

Sift4G

Benign

0.20

Polyphen

0.019

Vest4

0.39

MutPred

0.65

Gain of disorder (P = 0.0081)

MVP

0.36

MPC

0.73

ClinPred

0.14

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.47

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over