Variant 18-21532570-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_052911.3(ESCO1):c.2278A>G(p.Thr760Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ESCO1
NM_052911.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ESCO1	NM_052911.3 linkuse as main transcript	c.2278A>G	p.Thr760Ala	missense_variant	11/12	ENST00000269214.10	NP_443143.2
ESCO1	XM_011525798.2 linkuse as main transcript	c.2278A>G	p.Thr760Ala	missense_variant	11/12		XP_011524100.1
ESCO1	XM_011525799.4 linkuse as main transcript	c.2188A>G	p.Thr730Ala	missense_variant	10/11		XP_011524101.1
ESCO1	XM_047437285.1 linkuse as main transcript	c.2188A>G	p.Thr730Ala	missense_variant	10/11		XP_047293241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO1	ENST00000269214.10 linkuse as main transcript	c.2278A>G	p.Thr760Ala	missense_variant	11/12	1	NM_052911.3	ENSP00000269214	P1	Q5FWF5-1
ESCO1	ENST00000622333.1 linkuse as main transcript	c.274A>G	p.Thr92Ala	missense_variant	5/6	2		ENSP00000484873
ESCO1	ENST00000383276.1 linkuse as main transcript	c.*296A>G		3_prime_UTR_variant, NMD_transcript_variant	12/13	2		ENSP00000372763		Q5FWF5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251160

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135724

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727230

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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

Mar 18, 2024

The c.2278A>G (p.T760A) alteration is located in exon 11 (coding exon 8) of the ESCO1 gene. This alteration results from a A to G substitution at nucleotide position 2278, causing the threonine (T) at amino acid position 760 to be replaced by an alanine (A). 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

Uncertain

0.46

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.33

Sift

Benign

0.032

D;.

Sift4G

Uncertain

0.015

D;T

Polyphen

1.0

D;.

Vest4

0.43

MutPred

0.35

Loss of catalytic residue at T760 (P = 0.027);.;

MVP

0.75

MPC

2.1

ClinPred

0.98

GERP RS

5.5

Varity_R

0.67

gMVP

0.65

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