chr21-46302071-ATGGTGGTGGTGG-A

Variant names:

• chr21-46302071-ATGGTGGTGGTGG-A
• rs71318063
• NM_058180.5:c.885_896delCCACCACCACCA

Variant summary

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

The NM_058180.5(C21orf58):​c.885_896delCCACCACCACCA​(p.His296_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 0.000000738 in 1,355,332 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: C21orf58 NM_058180.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

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

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

• 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	c.885_896delCCACCACCACCA	p.His296_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.885_896delCCACCACCACCA	p.His296_His299del	disruptive_inframe_deletion	Exon 8 of 8	2	NM_058180.5	ENSP00000291691.8

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355332 Hom.: 0 AF XY: 0.00000150 AC XY: 1 AN XY: 667426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30746

American (AMR) AF: 0.00 AC: 0 AN: 32380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24366

East Asian (EAS) AF: 0.00 AC: 0 AN: 34164

South Asian (SAS) AF: 0.00 AC: 0 AN: 75964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 9.49e-7 AC: 1 AN: 1053752

Other (OTH) AF: 0.00 AC: 0 AN: 56290

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs71318063; hg19: chr21-47721985;