chr21-46287125-T-TAA

Variant names:

• chr21-46287125-T-TAA
• rs58271568
• NM_001314025.2:c.210+11_210+12dupAA

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+3insAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,506,712 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00057 (3 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 3 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+11_210+12dupAA		intron	N/A	NP_001300954.1	P58557-1
	YBEY	NM_058181.3		c.210+11_210+12dupAA		intron	N/A	NP_478061.1	P58557-1
	YBEY	NM_001314022.2		c.210+11_210+12dupAA		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+3insAA		splice_region intron	N/A	ENSP00000380813.4	P58557-1
	YBEY	ENST00000329319.7	TSL:1	c.210+2_210+3insAA		splice_region intron	N/A	ENSP00000329614.3	P58557-1
	YBEY	ENST00000339195.10	TSL:1	c.210+2_210+3insAA		splice_region intron	N/A	ENSP00000340675.6	P58557-2

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149394 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000290

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

GnomAD2 exomes AF: 0.00298 AC: 406 AN: 136068 AF XY: 0.00325

Gnomad AFR exome AF: 0.00146

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00130

Gnomad FIN exome AF: 0.00265

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00368

GnomAD4 exome AF: 0.000567 AC: 769 AN: 1357318 Hom.: 3 Cov.: 31 AF XY: 0.000609 AC XY: 410 AN XY: 672834

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

African (AFR) AF: 0.000338 AC: 10 AN: 29600

American (AMR) AF: 0.00159 AC: 50 AN: 31526

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 32 AN: 23144

East Asian (EAS) AF: 0.000192 AC: 7 AN: 36380

South Asian (SAS) AF: 0.000740 AC: 56 AN: 75680

European-Finnish (FIN) AF: 0.000780 AC: 38 AN: 48690

Middle Eastern (MID) AF: 0.000397 AC: 2 AN: 5042

European-Non Finnish (NFE) AF: 0.000523 AC: 550 AN: 1051290

Other (OTH) AF: 0.000429 AC: 24 AN: 55966

⚠️ 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: 0.00000669 AC: 1 AN: 149394 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72630

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

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

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

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 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: 67392

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

⚠️ 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: 0.00185 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

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;