Variant 18-21536085-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_052911.3(ESCO1):c.2144A>T(p.Asp715Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ESCO1
NM_052911.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.85

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESCO1	NM_052911.3 linkuse as main transcript	c.2144A>T	p.Asp715Val	missense_variant	10/12	ENST00000269214.10	NP_443143.2	Q5FWF5-1A0A024RC19
ESCO1	XM_011525798.2 linkuse as main transcript	c.2144A>T	p.Asp715Val	missense_variant	10/12		XP_011524100.1	Q5FWF5-1A0A024RC19
ESCO1	XM_011525799.4 linkuse as main transcript	c.2054A>T	p.Asp685Val	missense_variant	9/11		XP_011524101.1
ESCO1	XM_047437285.1 linkuse as main transcript	c.2054A>T	p.Asp685Val	missense_variant	9/11		XP_047293241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ESCO1	ENST00000269214.10 linkuse as main transcript	c.2144A>T	p.Asp715Val	missense_variant	10/12	1	NM_052911.3	ENSP00000269214.4	Q5FWF5-1
ESCO1	ENST00000622333.1 linkuse as main transcript	c.140A>T	p.Asp47Val	missense_variant	4/6	2		ENSP00000484873.1	A0A0C4DH04
ESCO1	ENST00000383276.1 linkuse as main transcript	n.*162A>T		non_coding_transcript_exon_variant	11/13	2		ENSP00000372763.1	Q5FWF5-2
ESCO1	ENST00000383276.1 linkuse as main transcript	n.*162A>T		3_prime_UTR_variant	11/13	2		ENSP00000372763.1	Q5FWF5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251310

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135820

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:

0.0000164

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727192

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jul 31, 2024

The c.2144A>T (p.D715V) alteration is located in exon 10 (coding exon 7) of the ESCO1 gene. This alteration results from a A to T substitution at nucleotide position 2144, causing the aspartic acid (D) at amino acid position 715 to be replaced by a valine (V). 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

0.90

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.88

MVP

0.82

MPC

2.5

ClinPred

0.97

GERP RS

5.5

Varity_R

0.77

gMVP

0.91

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