21-46302071-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGG

Variant names:

• chr21-46302071-A-ATGGTGG
• rs71318063
• NM_058180.5:c.891_896dupCCACCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_058180.5(C21orf58):​c.891_896dupCCACCA​(p.His298_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 0.00113 in 1,506,798 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: C21orf58 NM_058180.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

Genes affected

C21orf58 (HGNC:1300): (chromosome 21 open reading frame 58)

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_058180.5
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf58	NM_058180.5	c.891_896dupCCACCA	p.His298_His299dup	disruptive_inframe_insertion	Exon 8 of 8	ENST00000291691.12	NP_478060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf58	ENST00000291691.12	c.891_896dupCCACCA	p.His298_His299dup	disruptive_inframe_insertion	Exon 8 of 8	2	NM_058180.5	ENSP00000291691.8

Frequencies

GnomAD3 genomes AF: 0.000793 AC: 120 AN: 151408 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000609 AC: 68 AN: 111606 Hom.: 0 AF XY: 0.000677 AC XY: 41 AN XY: 60542

Gnomad AFR exome AF: 0.000177

Gnomad AMR exome AF: 0.000973

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000481

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000942

Gnomad OTH exome AF: 0.000300

GnomAD4 exome AF: 0.00117 AC: 1582 AN: 1355274 Hom.: 3 Cov.: 34 AF XY: 0.00117 AC XY: 778 AN XY: 667402

Gnomad4 AFR exome AF: 0.000293

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000585

Gnomad4 SAS exome AF: 0.000461

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.00138

Gnomad4 OTH exome AF: 0.000764

GnomAD4 genome AF: 0.000792 AC: 120 AN: 151524 Hom.: 0 Cov.: 0 AF XY: 0.000730 AC XY: 54 AN XY: 74004

Gnomad4 AFR AF: 0.000266

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71318063; hg19: chr21-47721985;