Genetic Variant YBEY:p.Thr61Ile (chr21-46287095-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001314025.2(YBEY):c.182C>T(p.Thr61Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

YBEY
NM_001314025.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2 link	c.182C>T	p.Thr61Ile	missense_variant	Exon 2 of 5	ENST00000397701.9	NP_001300954.1	P58557-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9 link	c.182C>T	p.Thr61Ile	missense_variant	Exon 2 of 5	2	NM_001314025.2	ENSP00000380813.4		P58557-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110564

Other (OTH)

AF:

0.00

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.182C>T (p.T61I) alteration is located in exon 2 (coding exon 1) of the YBEY gene. This alteration results from a C to T substitution at nucleotide position 182, causing the threonine (T) at amino acid position 61 to be replaced by an isoleucine (I). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;D;.;D

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

.;.;D;D

M_CAP

Uncertain

0.088

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

4.8

H;H;H;H

PhyloP100

7.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.8

D;D;D;D

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.98

MutPred

0.93

Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);

MVP

0.014

MPC

0.67

ClinPred

1.0

GERP RS

4.5

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.70

gMVP

0.91

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

21-46287095-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over