Genetic Variant CENPI:c.687+8C>T (chrX-101120792-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386188.2(CENPI):c.687+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,263 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

CENPI
NM_001386188.2 splice_region, intron

Scores

Splicing: ADA: 0.0001537

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.419

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

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	Effect	Exon Rank	Protein	UniProt
CENPI	NM_001386188.2	MANE Select	c.687+8C>T	splice_region intron	N/A	NP_001373117.1	Q92674-1
CENPI	NM_006733.3		c.687+8C>T	splice_region intron	N/A	NP_006724.2	Q92674-1
CENPI	NM_001318521.2		c.687+8C>T	splice_region intron	N/A	NP_001305450.1	A0A8C8KX99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CENPI	ENST00000682095.1	MANE Select	c.687+8C>T	splice_region intron	N/A	ENSP00000507927.1	Q92674-1
CENPI	ENST00000372927.5	TSL:5	c.687+8C>T	splice_region intron	N/A	ENSP00000362018.1	Q92674-1
CENPI	ENST00000684367.1		c.687+8C>T	splice_region intron	N/A	ENSP00000507595.1	Q92674-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083263

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

349109

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26131

American (AMR)

AF:

0.00

AC:

AN:

35132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19188

East Asian (EAS)

AF:

0.00

AC:

AN:

30038

South Asian (SAS)

AF:

0.00

AC:

AN:

53144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40361

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

829629

Other (OTH)

AF:

0.00

AC:

AN:

45541

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.6

(source)

DANN

Benign

0.37

PhyloP100

-0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.034

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

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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