NM_058180.5:c.894_896dupCCA

Variant names:

• chr21-46302071-A-ATGG
• rs71318063
• NM_058180.5:c.894_896dupCCA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_058180.5(C21orf58):​c.894_896dupCCA​(p.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 0.317 in 1,505,414 control chromosomes in the GnomAD database, including 68,153 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7315 hom., cov: 0)
  • Exomes 𝑓: 0.32 (60838 hom.)
• Consequence: C21orf58 NM_058180.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.565
• Publications: 12 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_058180.5
• BP6: Variant 21-46302071-A-ATGG is Benign according to our data. Variant chr21-46302071-A-ATGG is described in ClinVar as Benign. ClinVar VariationId is 402442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf58	NM_058180.5	MANE Select	c.894_896dupCCA	p.His299dup	disruptive_inframe_insertion	Exon 8 of 8	NP_478060.2
	C21orf58	NM_001286462.2		c.576_578dupCCA	p.His193dup	disruptive_inframe_insertion	Exon 8 of 9	NP_001273391.1	P58505-3
	C21orf58	NM_001286463.1		c.576_578dupCCA	p.His193dup	disruptive_inframe_insertion	Exon 7 of 7	NP_001273392.1	P58505-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf58	ENST00000291691.12	TSL:2 MANE Select	c.894_896dupCCA	p.His299dup	disruptive_inframe_insertion	Exon 8 of 8	ENSP00000291691.8	P58505-1
	C21orf58	ENST00000417060.5	TSL:1	c.780_782dupCCA	p.His261dup	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000402356.1	H7C1T9
	C21orf58	ENST00000397682.7	TSL:1	c.576_578dupCCA	p.His193dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000380798.3	P58505-3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45433 AN: 151342 Hom.: 7309 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.308 AC: 34405 AN: 111606 AF XY: 0.307

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.283

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.319 AC: 432147 AN: 1353956 Hom.: 60838 Cov.: 34 AF XY: 0.317 AC XY: 211234 AN XY: 666688

African (AFR) AF: 0.168 AC: 5157 AN: 30712

American (AMR) AF: 0.401 AC: 12936 AN: 32272

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5766 AN: 24314

East Asian (EAS) AF: 0.238 AC: 8111 AN: 34126

South Asian (SAS) AF: 0.299 AC: 22646 AN: 75756

European-Finnish (FIN) AF: 0.318 AC: 13367 AN: 42016

Middle Eastern (MID) AF: 0.237 AC: 1301 AN: 5482

European-Non Finnish (NFE) AF: 0.328 AC: 345594 AN: 1053038

Other (OTH) AF: 0.307 AC: 17269 AN: 56240

GnomAD4 genome AF: 0.300 AC: 45458 AN: 151458 Hom.: 7315 Cov.: 0 AF XY: 0.305 AC XY: 22551 AN XY: 73976

African (AFR) AF: 0.191 AC: 7903 AN: 41372

American (AMR) AF: 0.397 AC: 6045 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3464

East Asian (EAS) AF: 0.304 AC: 1551 AN: 5100

South Asian (SAS) AF: 0.323 AC: 1548 AN: 4786

European-Finnish (FIN) AF: 0.369 AC: 3876 AN: 10494

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22749 AN: 67734

Other (OTH) AF: 0.280 AC: 587 AN: 2094

Alfa AF: 0.203 Hom.: 491

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56
Mutation Taster		=83/17	polymorphism (auto)

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; COSMIC: COSV52448691; COSMIC: COSV52448691;