Variant 21-46291368-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001314025.2(YBEY):c.245T>G(p.Phe82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

YBEY
NM_001314025.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.156

Variant links:

Genes affected

YBEY (HGNC:1299): (ybeY metalloendoribonuclease) This gene encodes a highly conserved metalloprotein. A similar protein in bacteria acts as an endoribonuclease, and is thought to function in ribosomal RNA maturation and ribosome assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

YBEY links:

YBEY (HGNC:):

YBEY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056871623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YBEY	NM_001314025.2 linkuse as main transcript	c.245T>G	p.Phe82Cys	missense_variant	3/5	ENST00000397701.9	NP_001300954.1	P58557-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9 linkuse as main transcript	c.245T>G	p.Phe82Cys	missense_variant	3/5	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251352

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

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:

0.00000410

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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

Jun 17, 2024

The c.245T>G (p.F82C) alteration is located in exon 3 (coding exon 2) of the YBEY gene. This alteration results from a T to G substitution at nucleotide position 245, causing the phenylalanine (F) at amino acid position 82 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.034

T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.54

.;T;.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.017

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0040

B;B;B;B

Vest4

0.22

MutPred

0.41

Loss of stability (P = 0.0552);.;Loss of stability (P = 0.0552);Loss of stability (P = 0.0552);

MVP

0.014

MPC

0.22

ClinPred

0.021

GERP RS

-5.6

Varity_R

0.049

gMVP

0.53

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

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