20-13759800-C-T

Variant names:

• chr20-13759800-C-T
• rs1358244046
• NM_001276380.2:c.1720G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001276380.2(ESF1):​c.1720G>A​(p.Asp574Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. D574H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ESF1 NM_001276380.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2911791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESF1	NM_001276380.2	c.1720G>A	p.Asp574Asn	missense_variant	Exon 9 of 14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4	c.1720G>A	p.Asp574Asn	missense_variant	Exon 9 of 14		NP_057733.2
ESF1	XM_017027874.3	c.1720G>A	p.Asp574Asn	missense_variant	Exon 9 of 14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2	c.1720G>A	p.Asp574Asn	missense_variant	Exon 9 of 14	5	NM_001276380.2	ENSP00000480783.2
ESF1	ENST00000202816.5	c.1720G>A	p.Asp574Asn	missense_variant	Exon 9 of 14	5		ENSP00000202816.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444386 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718208

African (AFR) AF: 0.00 AC: 0 AN: 32186

American (AMR) AF: 0.00 AC: 0 AN: 40564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 38810

South Asian (SAS) AF: 0.00 AC: 0 AN: 82944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107262

Other (OTH) AF: 0.00 AC: 0 AN: 59768

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		3.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.11
Sift	Benign	0.072	T;.
Sift4G	Benign	0.22	T;T
Polyphen		1.0	D;.
Vest4		0.49
MutPred		0.13		Gain of MoRF binding (P = 0.038);.;
MVP		0.73
MPC		0.42
ClinPred		0.88	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.077
Mutation Taster		=89/11	polymorphism

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: rs1358244046; hg19: chr20-13740447;