Variant chr20-13759718-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276380.2(ESF1):c.1802T>C(p.Met601Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000953 in 1,574,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

ESF1
NM_001276380.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Variant links:

Genes affected

ESF1 (HGNC:15898): (ESF1 nucleolar pre-rRNA processing protein homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ESF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19484293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ESF1	NM_001276380.2 linkuse as main transcript	c.1802T>C	p.Met601Thr	missense_variant	9/14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4 linkuse as main transcript	c.1802T>C	p.Met601Thr	missense_variant	9/14		NP_057733.2
ESF1	XM_017027874.3 linkuse as main transcript	c.1802T>C	p.Met601Thr	missense_variant	9/14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2 linkuse as main transcript	c.1802T>C	p.Met601Thr	missense_variant	9/14	5	NM_001276380.2	ENSP00000480783	P1
ESF1	ENST00000202816.5 linkuse as main transcript	c.1802T>C	p.Met601Thr	missense_variant	9/14	5		ENSP00000202816	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000333

AC:

AN:

210484

Hom.:

AF XY:

0.0000434

AC XY:

AN XY:

115118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000269

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:

0.00000982

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000773

AC:

AN:

1422356

Hom.:

Cov.:

AF XY:

0.00000706

AC XY:

AN XY:

707744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000190

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:

0.00000363

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

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:

0.0000113

ExAC

AF:

0.0000165

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

Nov 14, 2023

The c.1802T>C (p.M601T) alteration is located in exon 9 (coding exon 8) of the ESF1 gene. This alteration results from a T to C substitution at nucleotide position 1802, causing the methionine (M) at amino acid position 601 to be replaced by a threonine (T). 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

0.39

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.27

Sift

Uncertain

0.025

D;.

Sift4G

Benign

0.12

T;T

Polyphen

0.97

D;.

Vest4

0.46

MVP

0.68

MPC

0.29

ClinPred

0.57

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.16

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