20-49084128-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001316.4(CSE1L):c.1585C>T(p.Leu529Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
CSE1L
NM_001316.4 missense
NM_001316.4 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
CSE1L (HGNC:2431): (chromosome segregation 1 like) Proteins that carry a nuclear localization signal (NLS) are transported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha binds the NLS, while importin-beta mediates translocation through the nuclear pore complex. After translocation, RanGTP binds importin-beta and displaces importin-alpha. Importin-alpha must then be returned to the cytoplasm, leaving the NLS protein behind. The protein encoded by this gene binds strongly to NLS-free importin-alpha, and this binding is released in the cytoplasm by the combined action of RANBP1 and RANGAP1. In addition, the encoded protein may play a role both in apoptosis and in cell proliferation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant where missense usually causes diseases, CSE1L
BP4
Computational evidence support a benign effect (MetaRNN=0.30632055).
BS2
High AC in GnomAdExome4 at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSE1L | NM_001316.4 | c.1585C>T | p.Leu529Phe | missense_variant | 15/25 | ENST00000262982.3 | |
CSE1L | NM_001362762.2 | c.1585C>T | p.Leu529Phe | missense_variant | 15/25 | ||
CSE1L | NM_001256135.2 | c.1417C>T | p.Leu473Phe | missense_variant | 14/24 | ||
CSE1L | NR_045796.2 | n.1223C>T | non_coding_transcript_exon_variant | 12/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSE1L | ENST00000262982.3 | c.1585C>T | p.Leu529Phe | missense_variant | 15/25 | 1 | NM_001316.4 | P1 | |
CSE1L | ENST00000396192.7 | c.1417C>T | p.Leu473Phe | missense_variant | 14/24 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251226Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135774
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461780Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727188
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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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 | Mar 01, 2024 | The c.1585C>T (p.L529F) alteration is located in exon 15 (coding exon 14) of the CSE1L gene. This alteration results from a C to T substitution at nucleotide position 1585, causing the leucine (L) at amino acid position 529 to be replaced by a phenylalanine (F). 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Benign
T;T
Polyphen
0.045
.;B
Vest4
MVP
MPC
0.51
ClinPred
T
GERP RS
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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