Variant X-101130051-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001386188.2(CENPI):c.1265T>G(p.Ile422Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000462 in 1,083,155 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

CENPI
NM_001386188.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPI	NM_001386188.2 linkuse as main transcript	c.1265T>G	p.Ile422Ser	missense_variant	13/22	ENST00000682095.1	NP_001373117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPI	ENST00000682095.1 linkuse as main transcript	c.1265T>G	p.Ile422Ser	missense_variant	13/22		NM_001386188.2	ENSP00000507927	P2	Q92674-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183084

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67558

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000462

AC:

AN:

1083155

Hom.:

Cov.:

AF XY:

0.00000572

AC XY:

AN XY:

349447

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000603

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

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 submitter

clinical testing

Ambry Genetics

Feb 02, 2024

The c.1265T>G (p.I422S) alteration is located in exon 12 (coding exon 11) of the CENPI gene. This alteration results from a T to G substitution at nucleotide position 1265, causing the isoleucine (I) at amino acid position 422 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

.;T;T

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.5

M;M;M

MutationTaster

Benign

0.60

N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.21

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.30

.;B;B

Vest4

0.64

MutPred

0.65

Loss of stability (P = 0.1092);Loss of stability (P = 0.1092);Loss of stability (P = 0.1092);

MVP

0.51

MPC

1.0

ClinPred

0.55

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over