21-46302071-A-ATGG

Position:

• chr21-46302071-A-ATGG

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_058180.5(C21orf58):​c.896_897insCCA​(p.His298dup) variant causes a 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 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.565

Genes affected

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

YBEY (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C21orf58	NM_058180.5	c.896_897insCCA	p.His298dup	inframe_insertion	8/8	ENST00000291691.12	NP_478060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf58	ENST00000291691.12	c.896_897insCCA	p.His298dup	inframe_insertion	8/8	2	NM_058180.5	ENSP00000291691	A2

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

GnomAD3 exomes AF: 0.308 AC: 34405 AN: 111606 Hom.: 3569 AF XY: 0.307 AC XY: 18604 AN XY: 60542

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 SAS exome AF: 0.301

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

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.307

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

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.280

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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;