20-13775883-C-A

Variant names:

• chr20-13775883-C-A
• rs758982975
• NM_001276380.2:c.1025G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001276380.2(ESF1):​c.1025G>T​(p.Arg342Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R342C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ESF1 NM_001276380.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESF1	NM_001276380.2	c.1025G>T	p.Arg342Leu	missense_variant	Exon 3 of 14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4	c.1025G>T	p.Arg342Leu	missense_variant	Exon 3 of 14		NP_057733.2
ESF1	XM_017027874.3	c.1025G>T	p.Arg342Leu	missense_variant	Exon 3 of 14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2	c.1025G>T	p.Arg342Leu	missense_variant	Exon 3 of 14	5	NM_001276380.2	ENSP00000480783.2
ESF1	ENST00000202816.5	c.1025G>T	p.Arg342Leu	missense_variant	Exon 3 of 14	5		ENSP00000202816.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		3.8
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Uncertain	0.39
Sift	Benign	0.053	T;.
Sift4G	Benign	0.25	T;T
Polyphen		0.38	B;.
Vest4		0.53
MutPred		0.39		Loss of disorder (P = 0.0551);.;
MVP		0.81
MPC		0.12
ClinPred		0.94	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.39
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs758982975; hg19: chr20-13756529;