20-49072400-ACA-GCC

Variant names:

• chr20-49072400-ACA-GCC
• NM_001316.4:c.883_885delACAinsGCC
• CSE1L p.Thr295Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001316.4(CSE1L):​c.883_885delACAinsGCC​(p.Thr295Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSE1L NM_001316.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSE1L	NM_001316.4	MANE Select	c.883_885delACAinsGCC	p.Thr295Ala	missense	N/A	NP_001307.2
	CSE1L	NM_001362762.2		c.883_885delACAinsGCC	p.Thr295Ala	missense	N/A	NP_001349691.1	P55060-3
	CSE1L	NM_001256135.2		c.769-168_769-166delACAinsGCC		intron	N/A	NP_001243064.1	P55060-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSE1L	ENST00000262982.3	TSL:1 MANE Select	c.883_885delACAinsGCC	p.Thr295Ala	missense	N/A	ENSP00000262982.2	P55060-1
	CSE1L	ENST00000889064.1		c.883_885delACAinsGCC	p.Thr295Ala	missense	N/A	ENSP00000559123.1
	CSE1L	ENST00000933032.1		c.883_885delACAinsGCC	p.Thr295Ala	missense	N/A	ENSP00000603091.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-47688937;