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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.308

AC:

34405

AN:

111606

Hom.:

3569

AF XY:

0.307

AC XY:

18604

AN XY:

60542

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 SAS exome

AF:

0.301

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

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.300

AC:

45458

AN:

151458

Hom.:

7315

Cov.:

AF XY:

0.305

AC XY:

22551

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.252

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.280

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over