21-46302477-A-C

Variant names:

• chr21-46302477-A-C
• rs1556337
• NM_058180.5:c.813+8T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058180.5(C21orf58):​c.813+8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C21orf58 NM_058180.5 splice_region, intron
• Scores: Splicing: ADA: 0.000008553
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 13 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf58	NM_058180.5	MANE Select	c.813+8T>G		splice_region intron	N/A	NP_478060.2
	C21orf58	NM_001286462.2		c.495+8T>G		splice_region intron	N/A	NP_001273391.1
	C21orf58	NM_001286463.1		c.495+8T>G		splice_region intron	N/A	NP_001273392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf58	ENST00000291691.12	TSL:2 MANE Select	c.813+8T>G		splice_region intron	N/A	ENSP00000291691.8
	C21orf58	ENST00000417060.5	TSL:1	c.699+8T>G		splice_region intron	N/A	ENSP00000402356.1
	C21orf58	ENST00000397682.7	TSL:1	c.495+8T>G		splice_region intron	N/A	ENSP00000380798.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.53
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000086
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1556337; hg19: chr21-47722391;