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.

21-46302071-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGG

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