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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

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

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_058180.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf58	NM_058180.5 link	c.888_896delCCACCACCA	p.His297_His299del	disruptive_inframe_deletion	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.888_896delCCACCACCA	p.His297_His299del	disruptive_inframe_deletion	Exon 8 of 8	2	NM_058180.5	ENSP00000291691.8		P58505-1

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

GnomAD3 exomes

AF:

0.0000986

AC:

AN:

111606

Hom.:

AF XY:

0.0000991

AC XY:

AN XY:

60542

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 SAS exome

AF:

0.000535

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151524

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000835

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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-ATGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over