Variant 18-21564297-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052911.3(ESCO1):c.1727C>T(p.Ser576Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,609,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESCO1
NM_052911.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Variant links:

Genes affected

ESCO1 (HGNC:24645): (establishment of sister chromatid cohesion N-acetyltransferase 1) Enables identical protein binding activity; peptide-lysine-N-acetyltransferase activity; and zinc ion binding activity. Involved in peptidyl-lysine acetylation; post-translational protein acetylation; and regulation of DNA replication. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ESCO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059800476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESCO1	NM_052911.3 linkuse as main transcript	c.1727C>T	p.Ser576Phe	missense_variant	7/12	ENST00000269214.10	NP_443143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO1	ENST00000269214.10 linkuse as main transcript	c.1727C>T	p.Ser576Phe	missense_variant	7/12	1	NM_052911.3	ENSP00000269214	P1	Q5FWF5-1
ESCO1	ENST00000383276.1 linkuse as main transcript	c.1727C>T	p.Ser576Phe	missense_variant, NMD_transcript_variant	7/13	2		ENSP00000372763		Q5FWF5-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245554

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457040

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

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.1727C>T (p.S576F) alteration is located in exon 7 (coding exon 4) of the ESCO1 gene. This alteration results from a C to T substitution at nucleotide position 1727, causing the serine (S) at amino acid position 576 to be replaced by a phenylalanine (F). 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

0.071

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.71

M_CAP

Benign

0.031

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.90

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.031

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.0090

Vest4

0.18

MVP

0.41

MPC

0.0087

ClinPred

0.95

GERP RS

4.0

Varity_R

0.14

gMVP

0.22

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.

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