Variant chr12-53269289-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012291.5(ESPL1):c.347C>T(p.Ala116Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,614,154 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.035 ( 295 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 325 hom. )

Consequence

ESPL1
NM_012291.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.55

Variant links:

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]

ESPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018171072).

BP6

Variant 12-53269289-C-T is Benign according to our data. Variant chr12-53269289-C-T is described in ClinVar as [Benign]. Clinvar id is 3056449.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESPL1	NM_012291.5 link	c.347C>T	p.Ala116Val	missense_variant	Exon 3 of 31	ENST00000257934.9	NP_036423.4	Q14674-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ESPL1	ENST00000257934.9 link	c.347C>T	p.Ala116Val	missense_variant	Exon 3 of 31	5	NM_012291.5	ENSP00000257934.4	Q14674-1
ESPL1	ENST00000553219.6 link	c.347C>T	p.Ala116Val	missense_variant	Exon 3 of 3	2		ENSP00000456450.2	H3BRX7
ESPL1	ENST00000552671.5 link	n.*278C>T		non_coding_transcript_exon_variant	Exon 3 of 31	2		ENSP00000447054.1	H3BM31
ESPL1	ENST00000552671.5 link	n.*278C>T		3_prime_UTR_variant	Exon 3 of 31	2		ENSP00000447054.1	H3BM31

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5341

AN:

152192

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.00923

AC:

2320

AN:

251250

Hom.:

137

AF XY:

0.00682

AC XY:

926

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00377

AC:

5518

AN:

1461842

Hom.:

325

Cov.:

AF XY:

0.00324

AC XY:

2354

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.00675

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00791

GnomAD4 genome

AF:

0.0351

AC:

5348

AN:

152312

Hom.:

295

Cov.:

AF XY:

0.0347

AC XY:

2587

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00695

Hom.:

129

Bravo

AF:

0.0400

ESP6500AA

AF:

0.119

AC:

523

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0112

AC:

1362

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ESPL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.80

T;T;.

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.1

D;N;N

REVEL

Benign

0.043

Sift

Benign

0.075

T;T;T

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.78

.;P;P

Vest4

0.26, 0.15

MPC

1.1

ClinPred

0.022

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.067

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over