Variant 18-21536044-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_052911.3(ESCO1):c.2185T>A(p.Trp729Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000356 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ESCO1
NM_052911.3 missense, splice_region

Scores

Splicing: ADA: 0.0001849

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27782124).

BS2

High AC in GnomAdExome4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ESCO1	NM_052911.3 linkuse as main transcript	c.2185T>A	p.Trp729Arg	missense_variant, splice_region_variant	10/12	ENST00000269214.10	NP_443143.2
ESCO1	XM_011525798.2 linkuse as main transcript	c.2185T>A	p.Trp729Arg	missense_variant, splice_region_variant	10/12		XP_011524100.1
ESCO1	XM_011525799.4 linkuse as main transcript	c.2095T>A	p.Trp699Arg	missense_variant, splice_region_variant	9/11		XP_011524101.1
ESCO1	XM_047437285.1 linkuse as main transcript	c.2095T>A	p.Trp699Arg	missense_variant, splice_region_variant	9/11		XP_047293241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO1	ENST00000269214.10 linkuse as main transcript	c.2185T>A	p.Trp729Arg	missense_variant, splice_region_variant	10/12	1	NM_052911.3	ENSP00000269214	P1	Q5FWF5-1
ESCO1	ENST00000622333.1 linkuse as main transcript	c.181T>A	p.Trp61Arg	missense_variant, splice_region_variant	4/6	2		ENSP00000484873
ESCO1	ENST00000383276.1 linkuse as main transcript	c.*203T>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000372763		Q5FWF5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250944

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135600

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000441

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000227

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

Mar 08, 2024

The c.2185T>A (p.W729R) alteration is located in exon 10 (coding exon 7) of the ESCO1 gene. This alteration results from a T to A substitution at nucleotide position 2185, causing the tryptophan (W) at amino acid position 729 to be replaced by an arginine (R). 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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.0049

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.37

N;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.16

Sift

Benign

0.074

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.56

P;.

Vest4

0.52

MutPred

0.41

Gain of solvent accessibility (P = 0.0374);.;

MVP

0.38

MPC

2.1

ClinPred

0.45

GERP RS

4.2

Varity_R

0.37

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.0040

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