chr12-53269955-A-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_012291.5(ESPL1):c.1013A>C(p.Glu338Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,614,056 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
ESPL1
NM_012291.5 missense
NM_012291.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.32
Genes affected
ESPL1 (HGNC:16856): (extra spindle pole bodies like 1, separase) Stable cohesion between sister chromatids before anaphase and their timely separation during anaphase are critical for chromosome inheritance. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms. The first step involves phosphorylation of STAG1 (MIM 604358) or STAG2 (MIM 300826) in the cohesin complex. The second step involves cleavage of the cohesin subunit SCC1 (RAD21; MIM 606462) by ESPL1, or separase, which initiates the final separation of sister chromatids (Sun et al., 2009 [PubMed 19345191]).[supplied by OMIM, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ESPL1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23342037).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPL1 | NM_012291.5 | c.1013A>C | p.Glu338Ala | missense_variant | 3/31 | ENST00000257934.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPL1 | ENST00000257934.9 | c.1013A>C | p.Glu338Ala | missense_variant | 3/31 | 5 | NM_012291.5 | P1 | |
ESPL1 | ENST00000552671.5 | c.*944A>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/31 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251190Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.0000371 AC XY: 27AN XY: 727248
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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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 | Feb 01, 2023 | The c.1013A>C (p.E338A) alteration is located in exon 3 (coding exon 2) of the ESPL1 gene. This alteration results from a A to C substitution at nucleotide position 1013, causing the glutamic acid (E) at amino acid position 338 to be replaced by an alanine (A). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Gain of catalytic residue at Y337 (P = 0.0188);Gain of catalytic residue at Y337 (P = 0.0188);
MVP
MPC
ClinPred
D
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