chr20-13766843-T-C

Position:

• chr20-13766843-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001276380.2(ESF1):​c.1600A>G​(p.Met534Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ESF1 NM_001276380.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.95

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESF1	NM_001276380.2	c.1600A>G	p.Met534Val	missense_variant	8/14	ENST00000617257.2	NP_001263309.1
ESF1	NM_016649.4	c.1600A>G	p.Met534Val	missense_variant	8/14		NP_057733.2
ESF1	XM_017027874.3	c.1600A>G	p.Met534Val	missense_variant	8/14		XP_016883363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESF1	ENST00000617257.2	c.1600A>G	p.Met534Val	missense_variant	8/14	5	NM_001276380.2	ENSP00000480783	P1
ESF1	ENST00000202816.5	c.1600A>G	p.Met534Val	missense_variant	8/14	5		ENSP00000202816	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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 22, 2022

The c.1600A>G (p.M534V) alteration is located in exon 8 (coding exon 7) of the ESF1 gene. This alteration results from a A to G substitution at nucleotide position 1600, causing the methionine (M) at amino acid position 534 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.21
Sift	Benign	0.53	T;.
Sift4G	Benign	0.62	T;T
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.32		Gain of sheet (P = 0.0344);.;
MVP		0.57
MPC		0.39
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13747490;