Genetic Variant C21orf58:p.His297_His299del (chr21-46302071-ATGGTGGTGG-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_058180.5(C21orf58):c.888_896delCCACCACCA(p.His297_His299del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,506,850 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 0.000040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

C21orf58
NM_058180.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_058180.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058180.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C21orf58	NM_058180.5	MANE Select	c.888_896delCCACCACCA	p.His297_His299del	disruptive_inframe_deletion	Exon 8 of 8	NP_478060.2
C21orf58	NM_001286462.2		c.570_578delCCACCACCA	p.His191_His193del	disruptive_inframe_deletion	Exon 8 of 9	NP_001273391.1	P58505-3
C21orf58	NM_001286463.1		c.570_578delCCACCACCA	p.His191_His193del	disruptive_inframe_deletion	Exon 7 of 7	NP_001273392.1	P58505-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C21orf58	ENST00000291691.12	TSL:2 MANE Select	c.888_896delCCACCACCA	p.His297_His299del	disruptive_inframe_deletion	Exon 8 of 8	ENSP00000291691.8	P58505-1
C21orf58	ENST00000417060.5	TSL:1	c.774_782delCCACCACCA	p.His259_His261del	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000402356.1	H7C1T9
C21orf58	ENST00000397682.7	TSL:1	c.570_578delCCACCACCA	p.His191_His193del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000380798.3	P58505-3

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000834

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000986

AC:

AN:

111606

AF XY:

0.0000991

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000856

AC:

116

AN:

1355326

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

667422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30746

American (AMR)

AF:

0.00

AC:

AN:

32382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24368

East Asian (EAS)

AF:

0.00

AC:

AN:

34164

South Asian (SAS)

AF:

0.00117

AC:

AN:

75960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1053750

Other (OTH)

AF:

0.000107

AC:

AN:

56290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151524

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.000835

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67752

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=133/67

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

21-46302071-ATGGTGGTGGTGG-ATGG

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