X-101148058-A-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001386188.2(CENPI):āc.1991A>Gā(p.Asp664Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,177,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000045 ( 0 hom., 1 hem., cov: 23)
Exomes š: 0.000031 ( 0 hom. 9 hem. )
Consequence
CENPI
NM_001386188.2 missense
NM_001386188.2 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 3.72
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.020357877).
BS2
High Hemizygotes in GnomAdExome4 at 9 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CENPI | NM_001386188.2 | c.1991A>G | p.Asp664Gly | missense_variant | 20/22 | ENST00000682095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CENPI | ENST00000682095.1 | c.1991A>G | p.Asp664Gly | missense_variant | 20/22 | NM_001386188.2 | P2 | ||
CENPI | ENST00000372927.5 | c.1991A>G | p.Asp664Gly | missense_variant | 19/21 | 5 | P2 | ||
CENPI | ENST00000684367.1 | c.1991A>G | p.Asp664Gly | missense_variant | 21/23 | P2 | |||
CENPI | ENST00000423383.3 | c.1991A>G | p.Asp664Gly | missense_variant | 20/21 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000446 AC: 5AN: 112102Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34266
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GnomAD3 exomes AF: 0.000121 AC: 18AN: 149163Hom.: 0 AF XY: 0.0000433 AC XY: 2AN XY: 46215
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GnomAD4 exome AF: 0.0000310 AC: 33AN: 1065009Hom.: 0 Cov.: 29 AF XY: 0.0000262 AC XY: 9AN XY: 343447
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GnomAD4 genome AF: 0.0000446 AC: 5AN: 112154Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1AN XY: 34328
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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 | Aug 02, 2023 | The c.1991A>G (p.D664G) alteration is located in exon 19 (coding exon 18) of the CENPI gene. This alteration results from a A to G substitution at nucleotide position 1991, causing the aspartic acid (D) at amino acid position 664 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at