chr20-13775211-C-A

Position:

• chr20-13775211-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001276380.2(ESF1):​c.1095G>T​(p.Leu365Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ESF1 NM_001276380.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESF1	NM_001276380.2	c.1095G>T	p.Leu365Phe	missense_variant	4/14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4	c.1095G>T	p.Leu365Phe	missense_variant	4/14		NP_057733.2
ESF1	XM_017027874.3	c.1095G>T	p.Leu365Phe	missense_variant	4/14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2	c.1095G>T	p.Leu365Phe	missense_variant	4/14	5	NM_001276380.2	ENSP00000480783	P1
ESF1	ENST00000202816.5	c.1095G>T	p.Leu365Phe	missense_variant	4/14	5		ENSP00000202816	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.1095G>T (p.L365F) alteration is located in exon 4 (coding exon 3) of the ESF1 gene. This alteration results from a G to T substitution at nucleotide position 1095, causing the leucine (L) at amino acid position 365 to be replaced by a phenylalanine (F). 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	0.54
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.9	H;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.91
MutPred		0.36		Gain of ubiquitination at K363 (P = 0.0982);.;
MVP		0.86
MPC		0.44
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.58
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13755857;