Variant 20-13775876-A-C 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.1032T>G(p.Asp344Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESF1
NM_001276380.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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=0.15583956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ESF1	NM_001276380.2 linkuse as main transcript	c.1032T>G	p.Asp344Glu	missense_variant	3/14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4 linkuse as main transcript	c.1032T>G	p.Asp344Glu	missense_variant	3/14		NP_057733.2
ESF1	XM_017027874.3 linkuse as main transcript	c.1032T>G	p.Asp344Glu	missense_variant	3/14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2 linkuse as main transcript	c.1032T>G	p.Asp344Glu	missense_variant	3/14	5	NM_001276380.2	ENSP00000480783	P1
ESF1	ENST00000202816.5 linkuse as main transcript	c.1032T>G	p.Asp344Glu	missense_variant	3/14	5		ENSP00000202816	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000840

AC:

AN:

238192

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000609

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446552

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000469

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 26, 2021

The c.1032T>G (p.D344E) alteration is located in exon 3 (coding exon 2) of the ESF1 gene. This alteration results from a T to G substitution at nucleotide position 1032, causing the aspartic acid (D) at amino acid position 344 to be replaced by a glutamic acid (E). 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

0.099

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.093

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.60

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.24

Sift

Benign

0.36

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.91

P;.

Vest4

0.16

MutPred

0.25

Gain of disorder (P = 0.1892);.;

MVP

0.71

MPC

0.070

ClinPred

0.31

GERP RS

3.0

Varity_R

0.042

gMVP

0.078

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