21-46287125-TA-T

Variant names:

• chr21-46287125-TA-T
• rs58271568
• NM_001314025.2:c.210+12delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000397701.9(YBEY):​c.210+3delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,489,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: YBEY ENST00000397701.9 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBEY	NM_001314025.2	c.210+12delA		intron_variant	Intron 2 of 4	ENST00000397701.9	NP_001300954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBEY	ENST00000397701.9	c.210+3delA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149396 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00112 AC: 1507 AN: 1340566 Hom.: 0 Cov.: 31 AF XY: 0.00119 AC XY: 791 AN XY: 664034

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00243 AC: 70 AN: 28824

American (AMR) AF: 0.00375 AC: 116 AN: 30918

Ashkenazi Jewish (ASJ) AF: 0.00220 AC: 50 AN: 22762

East Asian (EAS) AF: 0.00111 AC: 39 AN: 35078

South Asian (SAS) AF: 0.00265 AC: 195 AN: 73580

European-Finnish (FIN) AF: 0.00117 AC: 56 AN: 47888

Middle Eastern (MID) AF: 0.000201 AC: 1 AN: 4968

European-Non Finnish (NFE) AF: 0.000885 AC: 922 AN: 1041400

Other (OTH) AF: 0.00105 AC: 58 AN: 55148

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149396 Hom.: 0 Cov.: 0 AF XY: 0.0000413 AC XY: 3 AN XY: 72632

African (AFR) AF: 0.00 AC: 0 AN: 40690

American (AMR) AF: 0.00 AC: 0 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67392

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
Mutation Taster		=99/1	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: rs58271568; hg19: chr21-47707039; COSMIC: COSV52444718;