21-46287125-TAAA-TAAAA

Variant names:

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

Variant summary

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

The ENST00000397701.9(YBEY):​c.210+2_210+3insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,505,548 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: YBEY ENST00000397701.9 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

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

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 rank	MANE	Protein	UniProt
YBEY	NM_001314025.2	c.210+12dupA		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+2_210+3insA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.000469 AC: 70 AN: 149404 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000667

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.000206

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000742

Gnomad OTH AF: 0.000487

GnomAD4 exome AF: 0.000455 AC: 617 AN: 1356040 Hom.: 1 Cov.: 31 AF XY: 0.000472 AC XY: 317 AN XY: 672248

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.000953

Gnomad4 ASJ exome AF: 0.000562

Gnomad4 EAS exome AF: 0.00154

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.000305

Gnomad4 OTH exome AF: 0.000465

GnomAD4 genome AF: 0.000462 AC: 69 AN: 149508 Hom.: 0 Cov.: 0 AF XY: 0.000481 AC XY: 35 AN XY: 72754

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.0000666

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000782

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.000206

Gnomad4 NFE AF: 0.0000742

Gnomad4 OTH AF: 0.000483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58271568; hg19: chr21-47707039;