NM_058180.5:c.894_896delCCA

Variant names:

• chr21-46302071-ATGG-A
• rs71318063
• NM_058180.5:c.894_896delCCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_058180.5(C21orf58):​c.894_896delCCA​(p.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 0.00158 in 1,500,426 control chromosomes in the GnomAD database, including 18 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0057 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (6 hom.)
• Consequence: C21orf58 NM_058180.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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 Benign. Variant got -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_058180.5
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00575 (871/151518) while in subpopulation AFR AF= 0.0197 (815/41384). AF 95% confidence interval is 0.0186. There are 12 homozygotes in gnomad4. There are 408 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf58	NM_058180.5	c.894_896delCCA	p.His299del	disruptive_inframe_deletion	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.894_896delCCA	p.His299del	disruptive_inframe_deletion	Exon 8 of 8	2	NM_058180.5	ENSP00000291691.8

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 869 AN: 151402 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00483

GnomAD3 exomes AF: 0.00366 AC: 408 AN: 111606 Hom.: 1 AF XY: 0.00349 AC XY: 211 AN XY: 60542

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.00323

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.00301

Gnomad SAS exome AF: 0.00182

Gnomad FIN exome AF: 0.00377

Gnomad NFE exome AF: 0.00248

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00111 AC: 1504 AN: 1348908 Hom.: 6 AF XY: 0.00112 AC XY: 745 AN XY: 663956

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.000994

Gnomad4 EAS exome AF: 0.000648

Gnomad4 SAS exome AF: 0.000892

Gnomad4 FIN exome AF: 0.000980

Gnomad4 NFE exome AF: 0.000413

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.00575 AC: 871 AN: 151518 Hom.: 12 Cov.: 0 AF XY: 0.00551 AC XY: 408 AN XY: 74000

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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;