4-1056882-C-CG

Variant names:

• chr4-1056882-C-CG
• rs572675416
• NM_001366919.1:c.769dupC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001366919.1(RNF212):​c.769dupC​(p.Arg257ProfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 985,460 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (3 hom.)
• Consequence: RNF212 NM_001366919.1 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10

Genes affected

RNF212 (HGNC:27729): (ring finger protein 212) This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF212	NM_001366919.1	c.769dupC	p.Arg257ProfsTer20	frameshift_variant	Exon 11 of 12		NP_001353848.1
RNF212	XM_047450083.1	c.667dupC	p.Arg223ProfsTer20	frameshift_variant	Exon 9 of 10		XP_047306039.1
RNF212	XM_011513446.2	c.505dupC	p.Arg169ProfsTer20	frameshift_variant	Exon 6 of 7		XP_011511748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000698262.1	c.769dupC	p.Arg257ProfsTer20	frameshift_variant	Exon 11 of 12			ENSP00000513634.1
RNF212	ENST00000505693.5	n.696dupC		non_coding_transcript_exon_variant	Exon 5 of 6	5
RNF212	ENST00000508633.5	n.351dupC		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 509 AN: 152008 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000943

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00443 AC: 3692 AN: 833332 Hom.: 3 Cov.: 31 AF XY: 0.00437 AC XY: 1684 AN XY: 385050

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00117

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.00977

Gnomad4 NFE exome AF: 0.00463

Gnomad4 OTH exome AF: 0.00445

GnomAD4 genome AF: 0.00335 AC: 510 AN: 152128 Hom.: 2 Cov.: 33 AF XY: 0.00312 AC XY: 232 AN XY: 74384

Gnomad4 AFR AF: 0.000940

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.00580

Gnomad4 OTH AF: 0.00284

Bravo AF: 0.00277

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 62 Uncertain:1

Oct 10, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

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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: rs572675416; hg19: chr4-1050670;