Genetic Variant NM_001386188.2:c.644A>G (chrX-101120741-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001386188.2(CENPI):c.644A>G(p.Lys215Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,465 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

CENPI
NM_001386188.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34638843).

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.644A>G	p.Lys215Arg	missense	Exon 8 of 22	NP_001373117.1	Q92674-1
CENPI	NM_006733.3		c.644A>G	p.Lys215Arg	missense	Exon 7 of 21	NP_006724.2	Q92674-1
CENPI	NM_001318521.2		c.644A>G	p.Lys215Arg	missense	Exon 8 of 21	NP_001305450.1	A0A8C8KX99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPI	ENST00000682095.1	MANE Select	c.644A>G	p.Lys215Arg	missense	Exon 8 of 22	ENSP00000507927.1	Q92674-1
CENPI	ENST00000372927.5	TSL:5	c.644A>G	p.Lys215Arg	missense	Exon 7 of 21	ENSP00000362018.1	Q92674-1
CENPI	ENST00000684367.1		c.644A>G	p.Lys215Arg	missense	Exon 9 of 23	ENSP00000507595.1	Q92674-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1095465

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360913

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

35190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19342

East Asian (EAS)

AF:

0.00

AC:

AN:

30175

South Asian (SAS)

AF:

0.00

AC:

AN:

53849

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40467

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

839954

Other (OTH)

AF:

0.00

AC:

AN:

45993

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Benign

0.091

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.0043

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

4.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.99

REVEL

Benign

0.098

Sift

Benign

0.34

Sift4G

Benign

0.48

Polyphen

0.0030

Vest4

0.22

MutPred

0.71

Loss of methylation at K215 (P = 0.0131)

MVP

0.48

MPC

0.31

ClinPred

0.78

GERP RS

5.2

Varity_R

0.16

gMVP

0.20

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over