NM_001314025.2:c.464G>A

Variant names:

• chr21-46297594-G-A
• rs547409551
• NM_001314025.2:c.464G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001314025.2(YBEY):​c.464G>A​(p.Arg155Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,380,660 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.00018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00019 (4 hom.)
• Consequence: YBEY NM_001314025.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.918
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017912298).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2	c.464G>A	p.Arg155Gln	missense_variant	Exon 5 of 5	ENST00000397701.9	NP_001300954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9	c.464G>A	p.Arg155Gln	missense_variant	Exon 5 of 5	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152226 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000167 AC: 11 AN: 65706 AF XY: 0.000304

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000137

Gnomad ASJ exome AF: 0.000271

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000404

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000190 AC: 233 AN: 1228316 Hom.: 4 Cov.: 30 AF XY: 0.000217 AC XY: 130 AN XY: 598700

African (AFR) AF: 0.0000393 AC: 1 AN: 25416

American (AMR) AF: 0.000170 AC: 3 AN: 17648

Ashkenazi Jewish (ASJ) AF: 0.000105 AC: 2 AN: 19086

East Asian (EAS) AF: 0.0000354 AC: 1 AN: 28262

South Asian (SAS) AF: 0.000936 AC: 52 AN: 55584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43610

Middle Eastern (MID) AF: 0.00282 AC: 14 AN: 4968

European-Non Finnish (NFE) AF: 0.000140 AC: 138 AN: 984538

Other (OTH) AF: 0.000447 AC: 22 AN: 49204

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152344 Hom.: 0 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74492

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000302 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.0000916 AC: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.464G>A (p.R155Q) alteration is located in exon 5 (coding exon 4) of the YBEY gene. This alteration results from a G to A substitution at nucleotide position 464, causing the arginine (R) at amino acid position 155 to be replaced by a glutamine (Q). 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	0.092
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0090	T;.;T;.;.;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.78	.;T;.;T;T;T
MetaRNN	Benign	0.018	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;.;L;.;.;L
PhyloP100		0.92
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.42	N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.58	T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T
Polyphen		0.0080	B;B;B;B;B;B
Vest4		0.084
MVP		0.014
MPC		0.17
ClinPred		0.017	T
GERP RS		2.0
Varity_R		0.064
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs547409551; hg19: chr21-47717508;