Genetic Variant C21orf58:p.His299dup (chr21-46302071-A-ATGG) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_058180.5(C21orf58):c.894_896dupCCA(p.His299dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,505,414 control chromosomes in the GnomAD database, including 68,153 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7315 hom., cov: 0)

Exomes 𝑓: 0.32 ( 60838 hom. )

Consequence

C21orf58
NM_058180.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.565

Publications

12 publications found

Variant links:

Genes affected

C21orf58 (HGNC:1300): (chromosome 21 open reading frame 58)

C21orf58 links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_058180.5

BP6

Variant 21-46302071-A-ATGG is Benign according to our data. Variant chr21-46302071-A-ATGG is described in ClinVar as [Benign]. Clinvar id is 402442.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf58	NM_058180.5 link	c.894_896dupCCA	p.His299dup	disruptive_inframe_insertion	Exon 8 of 8	ENST00000291691.12	NP_478060.2	P58505-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf58	ENST00000291691.12 link	c.894_896dupCCA	p.His299dup	disruptive_inframe_insertion	Exon 8 of 8	2	NM_058180.5	ENSP00000291691.8		P58505-1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45433

AN:

151342

Hom.:

7309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.308

AC:

34405

AN:

111606

AF XY:

0.307

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.424

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.319

AC:

432147

AN:

1353956

Hom.:

60838

Cov.:

AF XY:

0.317

AC XY:

211234

AN XY:

666688

show subpopulations

African (AFR)

AF:

0.168

AC:

5157

AN:

30712

American (AMR)

AF:

0.401

AC:

12936

AN:

32272

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

5766

AN:

24314

East Asian (EAS)

AF:

0.238

AC:

8111

AN:

34126

South Asian (SAS)

AF:

0.299

AC:

22646

AN:

75756

European-Finnish (FIN)

AF:

0.318

AC:

13367

AN:

42016

Middle Eastern (MID)

AF:

0.237

AC:

1301

AN:

5482

European-Non Finnish (NFE)

AF:

0.328

AC:

345594

AN:

1053038

Other (OTH)

AF:

0.307

AC:

17269

AN:

56240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16330

32659

48989

65318

81648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.300

AC:

45458

AN:

151458

Hom.:

7315

Cov.:

AF XY:

0.305

AC XY:

22551

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.191

AC:

7903

AN:

41372

American (AMR)

AF:

0.397

AC:

6045

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3464

East Asian (EAS)

AF:

0.304

AC:

1551

AN:

5100

South Asian (SAS)

AF:

0.323

AC:

1548

AN:

4786

European-Finnish (FIN)

AF:

0.369

AC:

3876

AN:

10494

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22749

AN:

67734

Other (OTH)

AF:

0.280

AC:

587

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1583

3167

4750

6334

7917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.203

Hom.:

491

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.56

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

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

Publications

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21-46302071-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over