20-49074838-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001316.4(CSE1L):ā€‹c.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

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38
Variant links:
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]

Genome browser will be placed here

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
CSE1LNM_001316.4 linkuse as main transcriptc.1120T>G p.Leu374Val missense_variant 11/25 ENST00000262982.3 NP_001307.2 P55060-1A0A384NKW7
CSE1LNM_001362762.2 linkuse as main transcriptc.1120T>G p.Leu374Val missense_variant 11/25 NP_001349691.1
CSE1LNM_001256135.2 linkuse as main transcriptc.952T>G p.Leu318Val missense_variant 10/24 NP_001243064.1 P55060-4
CSE1LNR_045796.2 linkuse as main transcriptn.758T>G non_coding_transcript_exon_variant 8/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSE1LENST00000262982.3 linkuse as main transcriptc.1120T>G p.Leu374Val missense_variant 11/251 NM_001316.4 ENSP00000262982.2 P55060-1
CSE1LENST00000396192.7 linkuse as main transcriptc.952T>G p.Leu318Val missense_variant 10/245 ENSP00000379495.3 P55060-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250286
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135324
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460400
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726568
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
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 submitterclinical testingAmbry GeneticsJun 07, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.18
N;N
REVEL
Uncertain
0.41
Sift
Benign
0.19
T;D
Sift4G
Benign
0.17
T;T
Polyphen
0.93
.;P
Vest4
0.51
MutPred
0.84
.;Gain of glycosylation at S377 (P = 0.1439);
MVP
0.34
MPC
0.96
ClinPred
0.59
D
GERP RS
4.4
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.26
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1313352600; hg19: chr20-47691375; API