Genetic Variant C21orf58:p.His298_His299del (chr21-46302071-ATGGTGG-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_058180.5(C21orf58):c.891_896delCCACCA(p.His298_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 0.0000173 in 1,506,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

C21orf58
NM_058180.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.512

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.891_896delCCACCA	p.His298_His299del	disruptive_inframe_deletion	Exon 8 of 8	NP_478060.2
C21orf58	NM_001286462.2		c.573_578delCCACCA	p.His192_His193del	disruptive_inframe_deletion	Exon 8 of 9	NP_001273391.1	P58505-3
C21orf58	NM_001286463.1		c.573_578delCCACCA	p.His192_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.891_896delCCACCA	p.His298_His299del	disruptive_inframe_deletion	Exon 8 of 8	ENSP00000291691.8	P58505-1
C21orf58	ENST00000417060.5	TSL:1	c.777_782delCCACCA	p.His260_His261del	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000402356.1	H7C1T9
C21orf58	ENST00000397682.7	TSL:1	c.573_578delCCACCA	p.His192_His193del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000380798.3	P58505-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

111606

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1355198

Hom.:

AF XY:

0.0000135

AC XY:

AN XY:

667352

show subpopulations

African (AFR)

AF:

0.0000651

AC:

AN:

30738

American (AMR)

AF:

0.00

AC:

AN:

32370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24368

East Asian (EAS)

AF:

0.00

AC:

AN:

34150

South Asian (SAS)

AF:

0.0000263

AC:

AN:

75950

European-Finnish (FIN)

AF:

0.0000237

AC:

AN:

42156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1053682

Other (OTH)

AF:

0.0000178

AC:

AN:

56284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

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:

0.0000132

AC:

AN:

151408

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73878

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67760

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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

0.51

Mutation Taster

=146/54

polymorphism

(source)

Splicing

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

Publications

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21-46302071-ATGGTGGTGGTGG-ATGGTGG

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