1-173803202-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001387287.1(CENPL):c.724T>A(p.Ser242Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
CENPL
NM_001387287.1 missense
NM_001387287.1 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
CENPL (HGNC:17879): (centromere protein L) CENPL is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006) [PubMed 16622420].[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25932372).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CENPL | NM_001387287.1 | c.724T>A | p.Ser242Thr | missense_variant | 5/6 | ENST00000682279.1 | NP_001374216.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CENPL | ENST00000682279.1 | c.724T>A | p.Ser242Thr | missense_variant | 5/6 | NM_001387287.1 | ENSP00000507473 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251378Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135848
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461532Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727104
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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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 | May 03, 2023 | The c.862T>A (p.S288T) alteration is located in exon 6 (coding exon 4) of the CENPL gene. This alteration results from a T to A substitution at nucleotide position 862, causing the serine (S) at amino acid position 288 to be replaced by a threonine (T). 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
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
0.57
.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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