21-46287125-TAAA-TAAAAAAA

Variant names:

• chr21-46287125-T-TAAAA
• rs58271568
• NM_001314025.2:c.210+9_210+12dupAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000397701.9(YBEY):​c.210+2_210+3insAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,477,522 control chromosomes in the GnomAD database, including 86 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 0)
  • Exomes 𝑓: 0.028 (86 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 86 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397701.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBEY	NM_001314025.2	MANE Select	c.210+9_210+12dupAAAA		intron	N/A	NP_001300954.1	P58557-1
	YBEY	NM_058181.3		c.210+9_210+12dupAAAA		intron	N/A	NP_478061.1	P58557-1
	YBEY	NM_001314022.2		c.210+9_210+12dupAAAA		intron	N/A	NP_001300951.1	P58557-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBEY	ENST00000397701.9	TSL:2 MANE Select	c.210+2_210+3insAAAA		splice_region intron	N/A	ENSP00000380813.4	P58557-1
	YBEY	ENST00000329319.7	TSL:1	c.210+2_210+3insAAAA		splice_region intron	N/A	ENSP00000329614.3	P58557-1
	YBEY	ENST00000339195.10	TSL:1	c.210+2_210+3insAAAA		splice_region intron	N/A	ENSP00000340675.6	P58557-2

Frequencies

GnomAD3 genomes AF: 0.000415 AC: 62 AN: 149348 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000467

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000430

Gnomad OTH AF: 0.000487

GnomAD2 exomes AF: 0.0521 AC: 7088 AN: 136068 AF XY: 0.0529

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.0690

Gnomad ASJ exome AF: 0.0654

Gnomad EAS exome AF: 0.0279

Gnomad FIN exome AF: 0.0549

Gnomad NFE exome AF: 0.0578

Gnomad OTH exome AF: 0.0579

GnomAD4 exome AF: 0.0278 AC: 36879 AN: 1328070 Hom.: 86 Cov.: 31 AF XY: 0.0282 AC XY: 18578 AN XY: 658464

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

African (AFR) AF: 0.0107 AC: 314 AN: 29224

American (AMR) AF: 0.0442 AC: 1353 AN: 30600

Ashkenazi Jewish (ASJ) AF: 0.0359 AC: 809 AN: 22524

East Asian (EAS) AF: 0.00913 AC: 328 AN: 35922

South Asian (SAS) AF: 0.0221 AC: 1641 AN: 74206

European-Finnish (FIN) AF: 0.0395 AC: 1865 AN: 47246

Middle Eastern (MID) AF: 0.0226 AC: 112 AN: 4954

European-Non Finnish (NFE) AF: 0.0282 AC: 29000 AN: 1028684

Other (OTH) AF: 0.0266 AC: 1457 AN: 54710

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000415 AC: 62 AN: 149452 Hom.: 0 Cov.: 0 AF XY: 0.000426 AC XY: 31 AN XY: 72734

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

African (AFR) AF: 0.0000490 AC: 2 AN: 40800

American (AMR) AF: 0.000467 AC: 7 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.000580 AC: 2 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00216 AC: 21 AN: 9702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000430 AC: 29 AN: 67378

Other (OTH) AF: 0.000483 AC: 1 AN: 2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0213 Hom.: 259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

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;