20-49074838-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001316.4(CSE1L):āc.1120T>Gā(p.Leu374Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,400 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
CSE1L
NM_001316.4 missense
NM_001316.4 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 2.38
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSE1L | NM_001316.4 | c.1120T>G | p.Leu374Val | missense_variant | 11/25 | ENST00000262982.3 | NP_001307.2 | |
CSE1L | NM_001362762.2 | c.1120T>G | p.Leu374Val | missense_variant | 11/25 | NP_001349691.1 | ||
CSE1L | NM_001256135.2 | c.952T>G | p.Leu318Val | missense_variant | 10/24 | NP_001243064.1 | ||
CSE1L | NR_045796.2 | n.758T>G | non_coding_transcript_exon_variant | 8/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSE1L | ENST00000262982.3 | c.1120T>G | p.Leu374Val | missense_variant | 11/25 | 1 | NM_001316.4 | ENSP00000262982.2 | ||
CSE1L | ENST00000396192.7 | c.952T>G | p.Leu318Val | missense_variant | 10/24 | 5 | ENSP00000379495.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250286Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135324
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460400Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726568
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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 | Jun 07, 2024 | The c.1120T>G (p.L374V) alteration is located in exon 11 (coding exon 10) of the CSE1L gene. This alteration results from a T to G substitution at nucleotide position 1120, causing the leucine (L) at amino acid position 374 to be replaced by a valine (V). 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
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
0.93
.;P
Vest4
MutPred
0.84
.;Gain of glycosylation at S377 (P = 0.1439);
MVP
MPC
0.96
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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