chr21-46287125-T-TAAAAAAAA

Variant names:

• chr21-46287125-T-TAAAAAAAA
• rs58271568
• NM_001314025.2:c.210+5_210+12dupAAAAAAAA

Variant summary

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

The ENST00000397701.9(YBEY):​c.210+2_210+3insAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000092 in 1,359,226 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000092 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YBEY ENST00000397701.9 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• 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: 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+5_210+12dupAAAAAAAA		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+3insAAAAAAAA		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001314025.2	ENSP00000380813.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149398 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000920 AC: 125 AN: 1359226 Hom.: 0 Cov.: 31 AF XY: 0.0000905 AC XY: 61 AN XY: 673804

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

African (AFR) AF: 0.0000338 AC: 1 AN: 29626

American (AMR) AF: 0.000222 AC: 7 AN: 31562

Ashkenazi Jewish (ASJ) AF: 0.0000431 AC: 1 AN: 23184

East Asian (EAS) AF: 0.0000824 AC: 3 AN: 36386

South Asian (SAS) AF: 0.0000924 AC: 7 AN: 75760

European-Finnish (FIN) AF: 0.000164 AC: 8 AN: 48766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.0000931 AC: 98 AN: 1052866

Other (OTH) AF: 0.00 AC: 0 AN: 56026

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149398 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72636

African (AFR) AF: 0.00 AC: 0 AN: 40688

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: 0.00 AC: 0 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: 0.00 AC: 0 AN: 67396

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58271568; hg19: chr21-47707039;