Genetic Variant NM_001314025.2:c.210+12dupA (chr21-46287125-T-TA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001314025.2(YBEY):c.210+12dupA variant causes a 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. 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
NM_001314025.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.890

Publications

1 publications found

Variant links:

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]

YBEY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001314025.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.000469

AC:

AN:

149404

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000472

AC XY:

317

AN XY:

672248

show subpopulations

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

African (AFR)

AF:

0.00176

AC:

AN:

29498

American (AMR)

AF:

0.000953

AC:

AN:

31476

Ashkenazi Jewish (ASJ)

AF:

0.000562

AC:

AN:

23130

East Asian (EAS)

AF:

0.00154

AC:

AN:

36262

South Asian (SAS)

AF:

0.00123

AC:

AN:

75534

European-Finnish (FIN)

AF:

0.000431

AC:

AN:

48668

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

5036

European-Non Finnish (NFE)

AF:

0.000305

AC:

320

AN:

1050576

Other (OTH)

AF:

0.000465

AC:

AN:

55860

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.339

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000462

AC:

AN:

149508

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

AN XY:

72754

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

40804

American (AMR)

AF:

0.0000666

AC:

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.000782

AC:

AN:

5114

South Asian (SAS)

AF:

0.00126

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

9728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000742

AC:

AN:

67392

Other (OTH)

AF:

0.000483

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over